Developing a Heart Failure Polypill to Improve Outcomes at a Safety Net Hospital: A Pilot Crossover Randomized Controlled Trial
Phase: PHASE2
Conditions: Heart Failure With Reduced Ejection Fraction, HIV Infections
Sponsor: University of California, San Francisco

Developing a Heart Failure Polypill to Reduce Total Pill 
Burden Among People Living with HIV: A Pilot 
Crossover Randomized Controlled Trial
(COMBO HF-X)
University of California Institutional Review Board
Study #23-39360 Protocol Version 1.6
Approved September 11, 2023
ClinicalTrials.gov identifier: NCT06029712
Principal Investigators
Colette DeJong, MD
Matthew Durstenfeld, MD MAS
Priscilla Hsue, MD
Funding
UCSF CAPS-HIV Innovative Grant (P30MH062249), 
UCSF Center for AIDS Research, UCSF CFAR/ARI HIV 
Boost Award, and the National Center for Advancing 
Translational Sciences, National Institutes of Health, 
through UCSF-CTSI Grant Number UL1 TR001872.

Study Application (Version 1.6)
1.0
General Information
*Enter the full title of your study:
Developing a Heart Failure Polypill to Reduce Total Pill Burden: A Pilot Crossover Randomized 
Controlled Trial
*Enter the study alias:
Pilot Trial 
* This field allows you to enter an abbreviated version of the Study Title to quickly identify this
study.
2.0
Add departments
2.1 and Specify Research Location:
Is 
Primary? Department Name
UCSF - 
 - M_MED-CORE-CARD
138310
3.0
List the key study personnel: (Note: external and affiliated collaborators who 
are not in the UCSF directory can be identified later in the Qualifications of 
Key Study Personnel section at the end of the form)
3.1 *Please add a Principal Investigator for the study:
Dejong, Colette C
Select if applicable
Department Chair
Resident
Fellow
If the Principal Investigator is a Fellow, the name of the Faculty Advisor must be supplied below.
3.2 If applicable, please select the Research Staff personnel
A) Additional Investigators
Davis, Jonathan 
Other Investigator
Durstenfeld, Matthew S MD 
Other Investigator
Hickey, Matthew D MD, MD 
Other Investigator
Hsue, Priscilla MD, MD 
Co-Principal Investigator
Riley, Elise PhD 
N

 Other Investigator
Steward, Wayne PhD 
 Other Investigator
Zier, Lucas S 
 Other Investigator
B) Research Support Staff
Levkova, Marta 
 Study Coordinator
Li, Danny 
 Clinical Research Associate
Schaffer, Veronica 
 Study Coordinator
3.3 *Please add a Study Contact
 
Dejong, Colette C 
The Study Contact(s) will receive all important system notifications along with the Principal 
Investigator. (e.g. The project contact(s) are typically either the Study Coordinator or the Principal 
Investigator themselves).
3.4 If applicable, please add a Faculty Advisor/Mentor:
 
Hsue, Priscilla MD, MD
3.5 If applicable, please select the Designated Department Approval(s)
 
Hsue, Priscilla MD, MD 
Department Chair
Add the name of the individual authorized to approve and sign off on this protocol from your 
Department (e.g. the Department Chair or Dean).
4.0
 
Initial Screening Questions 
Updated Sept 2022 - Revised Common Rule (January 2018) Compliant / COVID-19 - 
v98
4.1  * 
:
PROJECT SUMMARY  (REQUIRED) Give a brief overview of this project (250 words or less). Tell us 
what this study is about, who is being studied, and what it aims to achieve. If you have an NIH 
Abstract, paste it here (Click on the orange question mark to the right for more detailed instructions):
A novel four-drug regimen for heart failure with reduced ejection fraction (HFrEF) extends 
patients’ life expectancy by an average of 6 years compared to traditional therapies, in addition to 
improving quality of life. Unfortunately, uptake of this complex multi-drug regimen has been low, 
especially among underserved communities with barriers to medication adherence. Although 
combination tablets have transformed access to care for conditions such as HIV and tuberculosis, 
no combination pill is available for HFrEF.
In the proposed study, we will partner with a pharmacy to package several heart failure 
medications into a single capsule (“polypill”) for patients living with HIV and HFrEF, with the goal 
of reducing total daily pill burden and improving adherence among PWH impacted by 

polypharmacy. In 
we will first conduct stakeholder interviews with patients, providers, 
Aim 1, 
and pharmacists to inform the design of a HFrEF polypill (separate IRB # 22-38189). In Aim 2 
, we will conduct a pilot, single-center, crossover randomized clinical 
(present IRB application)
trial to investigate whether, compared to usual care, a HFrEF polypill increases medication 
adherence among 40 adults with HFrEF. This pilot work will be funded by a grant from the UCSF 
CAPS-HIV Innovative Grant. Based on these findings, our group intends to submit a PCORI grant 
application to fund a larger RCT of cardiovascular polypills among people with HIV.
4.2  
 
*
:
HUD DEVICE (REQUIRED) 
 
Does this application involve a Humanitarian Use Device (HUD):
No 
Yes, and it includes a research component 
Yes, and it involves clinical care ONLY 
4.3  *
: 
TYPE OF RESEARCH (REQUIRED) 
(
Select the option that best fits your project Click the orange
question mark to the right for definitions and guidance):
Biomedical research (including medical records review, biospecimen collection and/or use, 
other healthcare or health outcomes related activities, research database, biospecimen bank, 
or recruitment registry) 
Social, behavioral, educational, and/or public policy research 
Hybrid - includes aspects of BOTH types of research (check this option if your research is 
mainly social/behavioral but also involves specimen collection or blood draws to look at 
biological measures) 
4.4  *
 
SUBJECT CONTACT: (REQUIRED) Does this study involve 
 contact or interactions with
ANY
participants:
Yes (including phone, email or web contact) 
No (limited to medical records review, biological specimen analysis, and/or data analysis) 
4.5  * RISK LEVEL: (REQUIRED) What is your estimation of the risk level, including all screening
:
procedures and study activities
Minimal risk 
Greater than minimal risk 
4.6  * REVIEW LEVEL: (REQUIRED) Requested review level (Click on the orange question mark to the
right for definitions and guidance):
Full Committee 
Expedited 
Exempt 
Generally, only 
studies require 
Greater than Minimal Risk 
Full 
. 
Committee Review We suggest you check 
 
Expedited Review
instead or change the risk level, if you checked the wrong box.
4.9  
 
* DATA/SPECIMEN ANALYSIS ONLY: (REQUIRED) Does this study 
 involve records review and
ONLY
/or biospecimen analysis (do not check 'Yes' if this is a registry, research or recruitment database, or
biospecimen repository):
  Yes  
  No
4.10  
 
* CLINICAL TRIAL: (REQUIRED)

Is this a clinical trial:
According to The World Health Organization (WHO) and the 
International Committee of Medical Journal Editors (ICMJE) a 
 
clinical trial is:
Any research study that prospectively assigns human participants or 
groups of humans to one or more health-related interventions to 
evaluate the effects on health outcomes.
ICMJE requires 
 of a clinical trial in a public database (such as 
registration
ClinicalTrials.gov) prior to enrollment, for eventual publication of results in 
member biomedical journals.
Public Law 110-85 requires that all investigators who perform 
Guidance: 
an 
 must ensure that the trial is registered on a 
applicable clinical trial
 
.
government web site called ClinicalTrials.gov
 
The FDA requires registration for 'applicable clinical trials,' defined 
as follows:
For any trials of drugs and biologics: controlled clinical investigations, 
other than Phase 1 investigations, of a product subject to FDA 
regulation.
For trials of biomedical devices: controlled trials with health outcomes 
of devices subject to FDA regulation, other than small feasibility 
studies, and pediatric post-market surveillance.
 
 
For additional information on the ClinicalTrials.gov registration process at 
UCSF and the definition of a clinical trial for purposes of registration, visit 
 
the ClinicalTrials.gov section of the UCSF Clinical Research Resource 
.
HUB
 
 
 Yes  
 No
 - 'NCT' number for this trial:
Clinical Trial Registration
NCT06029712
4.11  * 
: 
CLINICAL TRIAL PHASE (REQUIRED) Check the applicable phase(s):
Phase 0
Phase 1
Phase 1/2
Phase 2
Phase 2/3
Phase 3
Phase 4
Not Applicable
4.12  
: 
* INVESTIGATOR-INITIATED (REQUIRED) Is this an investigator-initiated study:
 Yes  
 No

 of the 
 to 
The UCSF IRB recommends use
Virtual Regulatory Binder
manage your study.
4.13  * 
 
CORONAVIRUS RESEARCH: (REQUIRED) Does this study involve research on coronaviruses (COVID-
19, SARS, MERS or other):
  Yes  
  No
4.15  
 
*
 
CANCER: (REQUIRED) Does this study involve cancer (e.g., the study involves patients with cancer 
or at risk for cancer, including behavioral research, epidemiological research, public policy research, 
specimen analysis, and chart reviews):
  Yes  
  No
4.16  * 
 
RADIATION EXPOSURE: (REQUIRED) Does your protocol involve any radiation exposure to patients
/subjects 
 from 
 
for 
 purposes (e.g., x-rays, CT-scans, DEXA, CT-
EITHER
standard care OR 
research
guided biopsy, radiation therapy, or nuclear medicine including PET, MUGA or bone scans):
  Yes  
  No
4.17  
 
* HIV SCREENING: (REQUIRED)Does this study involve screening for HIV infection:
You should answer 'Yes' if the protocol includes HIV testing even if it's just 
for screening to determine eligibility.
  Yes  
  No
4.18  *
 
 SCIENTIFIC REVIEW: (REQUIRED) If this study has undergone scientific or scholarly review, 
please indicate which entity performed the review (check all that apply):
Funding agency, cooperative group, study section or other peer-review process
Cancer Center Protocol Review Committee (PRC) (Full approval is required prior to final IRB 
approval for cancer-related protocols.)
CTSI Clinical Research Services (CRS) Advisory Committee
Departmental scientific review
CTSI Consultation Services
Other:
Has not undergone scientific/peer review
 
* Specify entity that provided review:  (REQUIRED)
UCSF CAPS-HIV Innovative Grant (funded project)
4.19  
 
* STEM CELLS: (REQUIRED)
 
Does this study involve
 
human stem cells (including iPS cells and adult 
stem cells), gametes or embryos:
No 
Yes, and requires IRB and GESCR review 
Yes, and requires GESCR review, but NOT IRB review 
4.20  
 
 
*
 
FINANCIAL INTERESTS: (REQUIRED) Do you or any other responsible personnel (or the spouse, 
 
 
registered domestic partner and/or dependent children thereof) have financial interests related to 
 
this study:

  Yes  
  No
5.0
 Funding
5.1  
 
* FEDERAL FUNDING: (REQUIRED) Is this study currently supported in whole or in part by Federal 
funding, 
, OR has it received 
 Federal funding in the past:
even by a subcontract
ANY
  Yes  
  No
5.2  
 
* 
Is this project linked in any way to the Department of Defense (DoD):
DoD INVOLVEMENT: 
(REQUIRED)
  Yes  
  No
5.3  SPONSORS:
External Sponsors: Identify all sponsors, funding sources, and 
entities that are contributing to the conduct of this study in a 
material way:
If funding comes from a Subcontract, please list only the Prime 
Sponsor (i.e. list “Bayer” instead of “Stanford University.”)
For drug and device donation agreements, select “Drug/Device 
Donation” under “Contract Type.”
For all studies with funding through UCSF, either the Award Number 
(A Number) OR the Proposal Number (P Number) is required (not 
 
both, even though they both display a red asterisk).
The A Number is preferred but may not be available when a 
new study is first submitted. 
The P Number is created by the UCSF Office of Clinical Trial 
 when they receive the study. If you don't 
Activation (OCTA)
have a P Number yet because the study has not yet been 
submitted to OCTA, send an email to 
.
clinicaltrials@ucsf.edu
If funds are awarded before IRB approval is obtained, please 
provide the A Number. 
If the submission is approved before the A Number is 
available, please provide the A Number the next time you 
submit changes to the Study Application but do not submit a 
Modification only to add the A Number. 
 
View 
Details
Sponsor Name
Sponsor Type
Awardee 
Institution:
Contract 
Type:
Project 
Number 
UCSF 
RAS 
System 
Award 
Number 
("A" + 
6 
digits) 
American College of 
Other (No 
funding 
comes 

Cardiology, Inc. 
05 
through 
UCSF C&G 
unit) 
 
 
 
Sponsor Name:
American College of Cardiology, Inc. 
Sponsor Type:
05 
Sponsor Role:
Funding
CFDA Number:
 
Grant/Contract Number:
 
Awardee Institution::
Other (No funding comes through UCSF C&G unit) 
Is Institution the Primary 
Grant Holder:
No 
if No, then who is the Primary 
Grantee?
Colette DeJong 
Contract Type:
 
Project Number:
 
UCSF RAS System Award 
Number ("A" + 6 digits):
 
Grant Number for Studies Not 
Funded thru UCSF:
 
Grant Title:
ACC/ABC Merck Research Fellowship Award (salary support 
for Colette DeJong) 
PI Name:
(If PI is not the same as 
identified on the study.)
 
Explain Any Significant 
Discrepancy:
 
Other Funding Sources and Unfunded Research - Gift, Program, 
Departmental or other Internal Funding (check all that apply):
Funded by gift (specify source below)
Funded by UCSF or UC-wide program (specify source below)
Specific departmental funding (specify source below)
Unfunded (miscellaneous departmental funding)
Unfunded student project
* Identify the gift, program, departmental, or other internal funding source: 
(REQUIRED)
CAPS-HIV Innovative Grant, CFAR-ARI HIV Research Boost Award
6.0
 Sites, Programs, Resources, and External IRB Review
6.1  
 
 (check all that apply): 
 UCSF AND AFFILIATED SITES
*
(REQUIRED)
UCSF Benioff Children's Hospital Oakland (BCH OAK)
UCSF Cancer Center Berkeley
UCSF Cancer Center San Mateo
UCSF China Basin clinics and facilities
UCSF Helen Diller Family Comprehensive Cancer Center
UCSF Langley Porter Psychiatric Institute (LPPI)
UCSF Medical Center at Mission Bay (Benioff Children's Hospital, the Betty Irene Moore 
Women's Hospital, Bakar Cancer Hospital, or outpatient clinics)

UCSF Mount Zion
UCSF Parnassus (Moffitt-Long hospital, dental clinics or other outpatient clinics)
UCSF Other Sites (including Laurel Heights and all the other sites outside the main hospitals 
and clinics)
UCSF Fresno
Gladstone Institutes
Institute on Aging (IOA)
Jewish Home
SF Dept of Public Health (DPH)
San Francisco VA Health Care System (SFVAHCS) – including Community-Based Outpatient 
Clinics (CBOCs)
Vitalant (formerly Blood Centers of the Pacific and Blood Systems Research Institute)
Zuckerberg San Francisco General (ZSFG)
Research involving SFDPH/ZSFG: A UCSF Research at SFDPH 
Protocol Application is required for all research. Review 
 
this link for 
more information and contact information for SFDPH/ZSFG 
questions. SFDPH sites and clinics have special requirements that 
you must be familiar with. The UCSF IRB will only review SFDPH 
IRB Applications with 
.
designated SFDPH PIs
6.2  
At what locations will study visits and activities occur: 
 LOCATIONS: 
*
(REQUIRED)
Zuckerberg San Francisco General Hospital – inpatient service, cardiology clinics, and Ward 86 
Positive Health Program
6.3  
Will any study procedures or tests be conducted off-site by non-UCSF 
OFF-SITE PROCEDURES: 
personnel:
  Yes  
  No
6.4  RESEARCH PROGRAMS: Check any UCSF research programs this study is associated with:
Cancer Center
Center for AIDS Prevention Sciences (CAPS)
Global Health Sciences
Immune Tolerance Network (ITN)
Neurosciences Clinical Research Unit (NCRU)
Osher Center
Positive Health Program
Weill Institute for Neurosciences Translational Research Unit (WIN TRU)
6.5  * CTSI CRS SERVICES: (REQUIRED)Will this study be carried out at one of the UCSF Clinical Research 
 Units or utilize CRS Service:
Services (CRS)
 Yes  
 No
6.6  * MULTI-CENTER TRIAL: (REQUIRED) Is this a multi-center or multi-site research trial:
By 
' we mean a study where the protocol is developed 
'multi-center trial
by an lead investigator, an industry sponsor, consortium, a disease-group, 
etc.,and multiple sites across the nation or in different countries participate 
in the trial. The local sites do not have any control over the design of the 
protocol.

  Yes  
  No
6.8  OTHER SITE TYPES: Check all the other types of sites not affiliated with UCSF with which you are 
cooperating or collaborating on this project:
Do NOT check any boxes below if this is a multi-center clinical trial, 
UCSF is just one of the sites, and neither UCSF nor one of its faculty-
linked affiliates (SF VAHCS, Gladstone, ZSFG) are the coordinating 
center.
Other UC Campus
Other institution
Other community-based site
Foreign Country
Sovereign Native American nation (e.g. Navajo Nation, Oglala Sioux Tribe, Havasupai, etc.)
6.11  * OUTSIDE RELIANCES: (REQUIRED) Are any of the collaborating sites requesting to rely on UCSF's 
IRB:
  Yes  
  No
6.15  * RELYING ON AN EXTERNAL IRB: (REQUIRED) Does this application include a request to rely on an 
external IRB (a central IRB (other than the NCI CIRB) or an external IRB (other UC campus, 
commercial, or institutional):
  Yes  
  No
7.0
 Outside Site Information
7.1  
 
Outside Site Information
If you have more than 10 sites to add, list the outside sites in the 
Outside Sites List document and upload it in the Other Study 
Documents section of the Initial Review Submission Packet form. 
Any sites requesting to rely on UCSF's IRB must be listed below. 
Click "Add a new row" to enter information for a site. Click it again to add a second site again to 
add a third site, a fourth site, etc.
Outside Site Information
Non-UCSF affiliated site information:
Site name:
Washington University in St. Louis

Contact name:
Justin Chen
Email:
justin.chen@wustl.edu
Phone:
314-792-0201
For Federally-funded studies only, corresponding FWA#:
 research at this site will be reviewed by:
* The
The non-affiliated site's IRB or a private IRB 
The non-affiliated site is requesting UCSF to be the IRB of 
record for this study 
The non-affiliated site is not engaged in the human subjects 
research and has provided a letter of support 
If the other site's IRB approval letter is available now, attach it to 
the application.  If the IRB approval letter is not yet available, 
submit it once you receive it. 
  
  Or, if the other site is 
 in human subjects 
 
not engaged
research, attach the letter of support to your application.
Outside Site Information
Non-UCSF affiliated site information:
Site name:
Daniel's Pharmacy
Contact name:
Iyad I. Nasrah, RPh
Email:
inasrah@gmail.com
Phone:
(415) 584-2210
For Federally-funded studies only, corresponding FWA#:
 research at this site will be reviewed by:
* The

The non-affiliated site's IRB or a private IRB 
The non-affiliated site is requesting UCSF to be the IRB of 
record for this study 
The non-affiliated site is not engaged in the human subjects 
research and has provided a letter of support 
If the other site's IRB approval letter is available now, attach it to 
the application.  If the IRB approval letter is not yet available, 
submit it once you receive it. 
  
  Or, if the other site is 
 in human subjects 
 
not engaged
research, attach the letter of support to your application.
8.0
 Research Plan and Procedures
8.1  
Describe the hypothesis or what the study hopes to prove: 
 HYPOTHESIS: 
*
(REQUIRED)
Compared with usual care, co-packaging of heart failure therapies into an over-encapsulated 
polypill will increase adherence to GDMT at 4 weeks and reduce total daily pill burden among 
patients with HIV and HFrEF.
8.2  
List the specific aims: 
 AIMS: 
*
(REQUIRED)
In the proposed study, we will utilize inexpensive over-encapsulation techniques to develop a 
HFrEF combination pill (“polypill”) for patients living with HFrEF, with and without HIV, with the 
goal of reducing total daily pill burden and improving adherence among PWH impacted by 
polypharmacy. 
To accomplish this, we will develop a clinical workflow through which participants’ HFrEF 
medications are over-encapsulated into a single, individualized polypill capsule at the pharmacy. 
Like a bubble pack, in which pharmacists sort a patient’s morning and evening doses into pre-
filled compartments to facilitate adherence, the polypill will be individualized to each patient and 
will not interfere with medication dosing or titration (Supplemental Figure). Thus, the proposed 
study is a medication packaging intervention, similar to a bubble pack. In a small pilot study, we 
will evaluate whether a HFrEF polypill improves adherence among adult patients with HFrEF at 
Zuckerberg San Francisco General Hospital (ZSFG). 
In 
 we will conduct formative interviews of patients, pharmacists, HIV primary care 
Aim 1,
clinicians, infection disease specialists, and cardiologists to characterize barriers to ART and GDMT 
adherence and elicit perspectives on a HFrEF polypill. This qualitative aim is covered by a 
separate CHR application (IRB # 22-38189).
 In 
, we will conduct a pilot, single-center, crossover randomized clinical trial to investigate 
Aim 2
whether, compared to usual care, a HFrEF polypill implementation strategy increases adherence 
to GDMT with no increase in serious adverse events among adults with HFrEF. We aim to recruit 
an HIV+ subgroup (~10-20 participants) and an HIV- subgroup (~10-20 participants). The 
estimated sample size will be 20-40, but we will plan from the onset to modify the total sample 
size in response to logistical constraints during this pilot study. Key secondary outcomes will 
include total daily pill burden, adherence to ART, and the Treatment Satisfaction Questionnaire for 
Medication, as well as feasibility measures around the polypill (cost, production time). This pilot 
study will not be powered for clinical outcomes, but exploratory outcomes will include heart 
failure admissions and the Kansas City Cardiomyopathy Questionnaire.
8.3  
Briefly describe the study design (e.g., observational, interventional, randomized, placebo-
 DESIGN: 
*
controlled, blinded, cross-over, cross-sectional, longitudinal, pharmacokinetic, etc.): (REQUIRED) 
Pilot phase II open-label randomized controlled trial with a 2x2 crossover design (AB/BA). The 
trial will examine whether over-encapsulation of several heart failure therapies into a single 
capsule is feasible and improves adherence and treatment satisfaction. Like a bubble pack or 

Medi-Set, the intervention is a delivery strategy for well-established, guideline-directed therapies 
for heart failure. 
8.4  
 Briefly provide the background and significance of this study (e.
 BACKGROUND AND SIGNIFICANCE:
*
g. why is this study needed) 
 
(space limit: one half page): (REQUIRED)
If this is a first in humans study, please summarize the safety data from 
the animal studies. For pediatric drug or device studies, please identify if 
this is the first study in pediatric populations.  
Reduction of total daily pill burden among PWH is associated with improved ART 
adherence and viral suppression, and has become a priority within HIV prevention and 
treatment. In an era of highly-effective treatments for HIV, medication acceptability and 
adherence have become key public health challenges. Pill burden has been identified as one of 
the most easily modifiable drivers of adherence to ART. The adverse effects of pill burden are 
amplified among patients with additional barriers to adherence, such as housing instability or 
stimulant use disorder. In a longitudinal study of people living with HIV who use drugs by Alvi et 
al, each additional pill was negatively associated with medication adherence (adjusted odds ratio 
of 0.87 per pill, 95% confidence interval 0.84-0.91). Single-tablet ART regimens have become 
1
first line, and long-acting injectable therapies have made viral suppression accessible to more 
patients. 
Pill burden among PWH declined with single-tablet ART, but has started to rise again 
due to comorbidities in an aging population.2 Over half of PWH in the U.S. are over 50, and 
non-ART medications now comprise the majority of daily pill burden for many PWH. In focus 
groups of patients and providers at ZSFG’s Golden Compass Clinic, management of comorbidities 
was a commonly cited issue, and interventions to support ART adherence were a shared priority 
of both patients and providers.  Total daily pill burden is rising faster among PWH than the 
3
general population, driven primarily by polypharmacy for cardiovascular and other comorbidities. 
PWH are at a two-fold increased risk of cardiovascular disease (CVD), which now accounts for 1 in 
5 deaths among PWH in the U.S. Polypharmacy can dilute the impact of single-tablet ART on total 
daily pill burden, leaving PWH at risk for pill fatigue and associated non-adherence.  
2
Heart failure with reduced ejection fraction (HFrEF) is one of the most serious 
cardiovascular comorbidities among PWH, with a five-year mortality of approximately 
50%. A four-drug regimen for HFrEF is highly effective, but significantly increases total 
daily pill burden among PWH. People with HIV are more likely to be diagnosed with HFrEF and 
more likely to die from heart failure, with the highest risk among patients with a detectable HIV 
viral load and patients who also use stimulants.
In a cohort study of 2,308 patients admitted to 
4 
an academic medical center in the Bronx with decompensated HFrEF, patients with HIV were at 
increased risk of cardiovascular mortality (28% vs. 15%) and all-cause mortality (41% vs. 26%) 
compared to non-infected individuals.  Patients with a detectable HIV viral load were at even 
4
higher risk of cardiovascular death (47%) and all-cause mortality (65%), and had a 70% risk of 
30-day readmission.
A four-drug regimen for HFrEF, referred to as guideline-directed medical therapy 
(GDMT), is associated with a 73% relative reduction in mortality at 2 years in addition 
to preventing hospital admissions and improving quality of life.6 Despite these benefits, 
the associated pill burden—ranging from 4-8 tablets per day—is a significant barrier to 
adherence, with an estimated 40-60% of patients with HFrEF missing a significant number of 
doses. By dramatically increasing total daily pill burden for PWH, polypharmacy related to heart 
failure can also increase the risk of non-adherence to ART.  In Alvi et al’s longitudinal study of 
2
PWH who use drugs, patients prescribed 5+ pills per day, including ART and non-ART 
medications, were half as likely to be adherent to their ART as those prescribed 4 pills or fewer 
(OR 0.54, 95% CI 0.40-0.72).  GDMT comprises at least 4 pills, placing patients at high risk for 
1
non-adherence even if they use single-tablet ART and no other medications.  In turn, non-
1
adherence is associated with hospital readmissions and increased mortality, as well as increased 
HIV viral load and risk of forward transmission. Pill burden and pill fatigue can manifest as spotty 
adherence or “drug holidays,” with serious implications for ART resistance patterns and HIV 
prevention. 
8.5  
Briefly summarize any preliminary studies relevant to your proposed 
PRELIMINARY STUDIES: 
research 
:
(space limit: one half page)

Despite compelling evidence that pill burden negatively impacts adherence, there is no 
combination pill for HFrEF available in the US, in part due to unclear commercial 
incentives. The standard 4-drug regimen for HFrEF comprises 2 inexpensive generics costing 
less than $10/month (a beta blocker and spironolactone), and 2 brand-name medications that 
both exceed $500/month (an SGLT2 inhibitor and twice-daily sacubitril-valsartan). SGLT2 
inhibitors and sacubitril-valsartan are manufactured by different companies, which lack a clear 
financial incentive to compound their medication with inexpensive generics. 
Over-encapsulation represents an inexpensive, efficient way to combine tablets into a 
single capsule for HFrEF, reducing total daily pill burden for patients with HIV 
cardiomyopathy. Over-encapsulated combination therapies have improved outcomes in other 
cardiovascular conditions, and can be used to evaluate the impact of combination therapy as 
groundwork for manufacturing a combination tablet. Polypills have proven to be a feasible and 
. A trial of 303 
effective intervention to improve medication adherence in low-resource settings
patients in Alabama employed over-encapsulation methods to combine medications for 
cholesterol and hypertension into a single capsule.  The investigators found over-encapsulation to 
7
be feasible, affordable, and acceptable to patients, and the polypill resulted in significantly lower 
systolic blood pressure and cholesterol.  Polypills have also been shown to improve adherence 
7
and reduce mortality in patients with a history of myocardial infarction (MI).  In the 2022 
8
SECURE trial, a polypill was associated with a 33% relative reduction in mortality among patients 
with a recent MI.  
8
All once-daily HFrEF medications can be packaged into a single small capsule 
(Supplemental Figure), reducing patients’ pill burden while avoiding the manufacturing 
and financial hurdles that have prevented a HFrEF polypill from coming to market. There 
is another single-center study of a HFrEF polypill currently recruiting in Houston, Texas, using 
similar over-encapsulation methods in a general HFrEF population.  If these early studies are 
9
successful, a HFrEF polypill intervention could be continued at ZSFG, and replicated for other HIV-
associated comorbidities. Furthermore, SGLT2 inhibitors will go off-patent in 2025. If polypills are 
shown to improve clinical outcomes, generic manufacturers or public payors, such as California’s 
Medi-Cal Rx, would have incentive to manufacture a generic HFrEF combination tablet. 
8.6  
Is this a treatment study, i.e. does this study intend to provide treatment
* TREATMENT PROTOCOL: 
to individuals with a medical or psychological condition: (REQUIRED)
 Yes  
 No
8.7  
 Does this study involve any procedures, lab tests or imaging studies that
* BILLABLE PROCEDURES:
have a CPT code and could be billable to patients, their insurance, Medi-Cal, Medicare, or any other
entity (answer 'Yes' even if the study is going to pay for all the procedures): (REQUIRED)
 Yes  
 No
8.8  
Types of research activities that will be carried out. Check all that
COMMON RESEARCH ACTIVITIES: 
*
apply and describe in more detail in the 'Procedures / Methods' section: (REQUIRED)
Interviews, questionnaires, surveys
Educational or cognitive tests
Focus groups
Social media-based research activities
Observation
Fitness tests or other exertion activities
Use of mobile health apps or other apps
Collection of data from wearable tech such as Fitbit, Apple Watch, Garmin, motion actigraphs, 
etc.)
Non-invasive imaging or testing (MRI, EEG, pulse oximetry, etc.)
Imaging procedures or treatment procedures that involve radiation (x-rays, CT scans, CT-
guided biopsies, DEXA scans, MUGA or PET scan)
Administration of contrast agent
Randomization to one intervention versus another

Use of placebo
Biopsy conducted solely for research purposes
Sham surgical procedure
None of the above
8.9  
PROCEDURES / METHODS: 
* 
(REQUIRED)
For clinical research, list all study procedures, tests and treatments 
required for this study, including when and how often they will be 
performed. If there are no clinical procedures, describe the research 
activities.
 
If some of the activities would occur even if the person were not in the 
study, as in the case of treatment or tests performed for diagnostic 
purposes, clearly differentiate between those activities that will be 
done solely for research purposes and those that are happening as 
part of routine care.
 
Examples may include:
additional scans outside standard clinical diagnosis or monitoring
additional biopsies to collect tissue for research
extra clinic visits
extra lab tests not required for clinical care
If you have a procedure table, attach it to the submission with your 
other study documents.
Aim 1 (qualitative; separate IRB # 22-38189). Conduct formative interviews of patients, 
pharmacists, HIV primary care and infectious disease providers, and cardiologists to characterize 
barriers to medication adherence and elicit perspectives on a HFrEF polypill to reduce total daily 
pill burden among PWH.
Aim 2 (the focus of this CHR application). Investigate whether over-encapsulation of 
several heart failure medications into a single capsule (“polypill”) is feasible and 
improves adherence among 20-40 adults with HFrEF, with or without HIV, using a 
single-center, crossover RCT design. 
Hypothesis: Compared with usual care, a HFrEF polypill implementation strategy will increase 
adherence to GDMT 4 weeks and reduce total daily pill burden among patients with HFrEF. 
Rationale:HFrEF among PWH is associated with a high pill burden, which adversely impacts 
adherence. Over-encapsulation is an inexpensive and replicable method to co-package several 
tablets into a single capsule at the level of the pharmacy. However, the role of over-encapsulation 
to reduce pill burden among adults with HIV and HFrEF is unknown. 
Design:Pilot phase II open-label randomized trial with a 2x2 crossover design (AB/BA)
Recruitment:The research team will identify potential participants using existing clinical lists 
within our divisions (the Epic Heart Failure registry, the cardiology and Ward 86 clinic lists, and 
the cardiology and family medicine inpatient lists). DPH clinicians (i.e. cardiovascular clinical 
pharmacist Christina Wang) will pre-approve the use of Epic reports or Epic lists of potential 
participants prior to contacting them for recruitment for the study. Customized columns in Epic 
lists (for example, age, renal function, HIV status, contact information) will be used to screen 
potentially eligible participants without opening their chart. In some cases, researchers may want 
to open the patient's chart to review their eligibility prior to contacting the patient for recruitment 
& consent. In these cases, researchers will get approval from the patient's own healthcare 
provider prior to opening their chart to screen for study eligibility.
Eligibility: Participants will be eligible if they are ≥ 18 years old and carry a diagnosis of heart 
failure, with prior chart evidence of reduced ejection fraction (i.e., prior echocardiogram or MRI 
with ejection fraction ≤50%). Given that our pharmacy partner in this over-encapsulation study is 
Daniel’s Pharmacy, we will only include participants who can conveniently obtain their 
medications through one of 3 available mechanisms (mail, pick up at a ZSFG clinic, or pick up at 
Daniel’s pharmacy). At an initial screening visit (week T-1), participants will be asked to provide 

informed consent. Their current heart failure regimen will be reviewed. If they are not prescribed 
all four classes of GDMT, and do not have contraindications, additional agents will be prescribed 
by the study clinician if determined to be clinically appropriate. 
At the first trial visit (week 0), labs will be checked if clinically indicated after starting new 
medications. Additional guideline-directed medications may be started if there are no 
contraindications. During this visit, participants will be randomized to the AB group or BA group 
using REDcap. The run-in period will consist of the screening visit and the first trial visit (week 0). 
Potential participants who do not attend these two initial visits will not be enrolled in the trial and 
will not receive the intervention. The goal of this is to ensure that patients who start the 
intervention are likely to present for follow-up, especially given the importance of monitoring 
patients for safety metrics and medication-related adverse effects.
Intervention:The intervention will be pharmacy-level over-encapsulation of once-daily heart 
failure medications (beta-blocker, SGLT2 inhibitor, spironolactone, and ACE/ARB/ARNI) into a 
single capsule. For some patients, other once-daily cardiovascular medications, such as a diuretic, 
may be included if capsule size allows (otherwise, these medications will continued to be filled 
separate to the polypill, as individual tablets). If the patient uses a twice-daily ARNI medication, 
the morning dose may be included in the polypill and the PM dose will continue to be dispensed 
separately. We will partner with Daniel’s Pharmacy, a local community pharmacy with proficiency 
in over-encapsulation and over 20 years’ experience working with ZSFG to deliver adherence 
interventions. 
Polypill Description:
For patients in the polypill arm, heart failure medications will be filled as usual, but rather than 
dispensing each medication separately, the pharmacy technician will hand-pack all once-daily 
heart failure medications into a small plastic capsule (Supplemental Figure). The doses will be 
individualized to the patient based on their physician’s prescription. Thus, the polypill will be a 
late-stage implementation intervention to reduce pill burden, without restricting dose possibilities 
or interfering with medication titration. We are requesting an IND exempt determination from the 
UCSF IRB, given that the proposed intervention involves repackaging of FDA-approved 
medications without significantly changing their risk profile nor seeking additional indications (see 
the Drugs section of this application). This is similar to an IND exemption received by co-
investigator Dr. Mark Huffman for the NHLBI-funded QUARTET-USA trial of a hypertension 
polypill. 
Visit Schedule and Randomization:
Patients will first attend an intake visit (week T-1), where eligibility will be reviewed, informed 
consent will be obtained, baseline labs and patient questionnaires will be collected, and additional 
GDMT agents may be prescribed by the study clinician if clinically indicated and there are no 
contraindications. As part of the consent, we will also ask participants' permission to contact their 
primary outpatient providers. For participants that have a medication support person (e.g. a 
home nurse, building nurse or adult family member who manages their medications), we will ask 
permission to contact that person during the study period to ensure safe transitions in medication 
doses or packaging. 
At the first trial visit (week 0), labs will be rechecked if clinically indicated, and additional GDMT 
agents may prescribed if clinically indicated, with the goal of all participants being prescribed 
guideline-directed quad therapy for HFrEF prior to randomization if there are no contraindications.
 The study team will also check if the participant has any video conferencing capability 
11
(WhatsApp, FaceTime, or Zoom) to facilitate virtual pill counts, and if not, the study team will 
offer to help the participant set this up. The study team will send a message to the patient's 
primary outpatient providers in order to update the care team with any medication changes and 
to create a line of communication for any issues or concerns that may arise. Study participants 
will be encouraged to contact the study team with any issues specifically related to their heart 
failure medications during the study period, and to contact their regular doctors about any other 
clinical concerns. If the study team is contacted about other issues (e.g. new heart failure 
symptoms), we will conduct clinical triage and refer the participant to the ER, urgent care, and/or 
their primary doctors as clinically indicated.  
During the first trial visit (week 0), half of participants will be randomized to the AB group 
(polypill for 4 weeks, then individual tablets for 4 weeks). The other half of participants will be 
randomized to the BA group (individual tablets for 4 weeks, then polypill for 4 weeks). This follow-
up period is comparable to that of the pilot crossover trial that preceded QUARTET-USA (4 weeks 
in a polypill arm and 4 weeks in a placebo arm). 
After randomization, participants assigned to receive the polypill up-front will be delivered 30-day 
supplies of the polypill via their preferred delivery method (mail, pick up at a ZSFG clinic, or pick 
up at Daniel’s Pharmacy). Participants assigned to usual care will be mailed or pick up their 
existing heart failure medications as individual pills. The screening visit and first trial visit may be 
timed by study clinicians based on when the participant's heart failure medications will be ready 
for a refill according to insurance.
At trial follow-up visits at 4 and 8 weeks, participants will be assessed for outcomes and adverse 
events and will undergo lab monitoring as clinically indicated. Patients will be asked to bring in 
their pill bottles and/or MediSets or bubble packs. Please see the attached Schedule of Study 
Visits. Medication doses may be titrated at these visits if clinically indicated. Participants in the AB 

and BA arms will have the same follow-up schedule, and can opt to receive refills of their 
medications by mail, at the pharmacy, or in clinic. Any new starts of guideline-directed heart 
failure medications that are included in the polypill will be continued as individual pills when the 
polypill group crosses over to the individual tablet condition, and/or when the trial concludes. All 
participants will be referred to cardiology clinic, if not already established there, for ongoing 
management of their heart failure therapies after the trial.  
Participants will receive $10 gift certificates for each visit, with an additional $30 if they bring in 
their pill bottles and an additional $10 if blood draws are needed. Bus tokens, parking vouchers, 
or other transportation vouchers will also be provided. At the conclusion of the study, we will 
perform semi-structured exit interviews with participants, clinicians, and pharmacists. We will use 
prepared interview guides, and will offer $20 reimbursement for participation in a 30-60 minute 
exit interview. We will elicit stakeholders’ experiences with the polypill, barriers encountered, 
preferences for trade-offs between pill size and number of pills, perceptions about taking polypills 
vs. the individual components, and experience working with the pharmacy for medication 
delivery. 
 
Outcomes: The primary outcome will be adherence to overall and individual components of 
GDMT at 4 and 8 weeks, as measured by pill count. If participants do not bring their pill bottles to 
the visit, we will try to reschedule within the next few days before the 30-day supply is 
completed. If it is not possible to reschedule, the study team will ask to have a video chat with 
the patient (FaceTime, WhatsApp or Zoom) in order to complete a virtual pill count over video 
call. If none of these are possible, the primary outcome will not be collected for that time point. 
Secondary outcomes will include number of evidence-based heart failure therapies prescribed, 
number of dose increases or achieved doses of heart failure therapies, MMAS-8 adherence 
questionnaire, self-reported adherence to GDMT and other medications, treatment satisfaction 
using the Treatment Satisfaction Questionnaire for Medication, and documented episodes of 
treatment-related adverse effects (e.g. allergy, hyperkalemia, or bradycardia). We will also 
capture feasibility metrics in conjunction with Daniel’s Pharmacy, including production time and 
costs for polypill packaging.  As a pilot trial, our study will not be powered for clinical outcomes, 
but key exploratory outcomes will include HFrEF admissions, change in BNP or NT-ProBNP (a 
measure of clinical heart failure status), blood pressure, heart rate, and change in health-related 
quality of life measured by the Kansas City Cardiomyopathy Questionnaire. The exit interviews 
will be transcribed, coded, and analyzed using the CFIR Framework for evaluation of an 
implementation project. 
In addition to the in-person study visits (screening, 0, 4, and 8 weeks), we will perform telephone 
visits with participants at approximately 2 and 6 weeks. At these telephone check-ins, we will 
screen for adverse events and order monitoring labs if clinically indicated according to the study 
team's discretion. 
Clinical Tests and Treatments: At monthly follow-up visits, we will monitor standard vital signs 
(heart rate, blood pressure, and oxygen saturation) and standing weight, as is routine for a 
cardiology clinic visit. Participants will also undergo lab monitoring at least every 2 months or as 
clinically indicated, including a basic metabolic panel to monitor potassium and creatinine levels 
while on heart failure medications. We will also measure a BNP or NT-proBNP at baseline, 4 
weeks, and 8 weeks (laboratory measure of heart failure status).   
Exit interviews: We will conduct 30-60 minute semi-structured exit interviews, using interview 
guides prepared using the Consolidated Framework for Implementation Research. Qualitative data 
will be audiotaped and transcribed verbatim using Qualtranscribe or secure Zoom or OneDrive 
transcription services. Dedoose software will be used to assist the investigative team with 
organizing, coding, and analyzing the qualitative data. The de-identified transcribed data will then 
be available for team members for coding and analysis. The coding team for interviews will 
consist of Dr. Colette DeJong and Dr. Matthew Durstenfeld from UCSF, Dr. Justin Chen and Dr. 
Anubha Agarwal from Washington University in St. Louis, and one research assistant, with 
mentorship from Drs. Priscilla Hsue and Wayne Steward. We will deploy a Framework Analysis 
approach to analyze our data.
Limitations: Our study is designed as a small pilot trial, and thus, will not be powered for clinical 
outcomes such as heart failure admissions. Our primary outcomes are feasibility and adherence. 
Adherence can be challenging to measure; however, we will use well-validated tools including pill 
counts and the MMAS-8 questionnaire. We selected a crossover trial design because it allows for 
efficient comparison of treatment arms in a small study population, and because the use of each 
participant as his/her own matched control will minimize unmeasured confounders. This study 
design carries risk of carryover effects, wherein participants remain impacted by the prior 
treatment after crossing over. Since one arm is standard delivery of medications as individual 
tablets, we expect that these carryover effects will be minimal, and we will include treatment 
order as a variable in our regression models.
Data and Samples to be Collected:
Blood draw: Standard venipuncture will be performed on patients with < 10ml taken at each 
blood draw. Patients will undergo serial potassium and creatinine monitoring, as well as BNP or 
NT-proBNP monitoring.

1.  
2.  
3.  
Study follow-up: participants will complete monthly follow-up visits with Dr. DeJong or a clinical 
research assistant (weeks 0, 4, and 8). At these visits, they will be asked to provide their 
medication supply for pill count, and will be screened for any treatment-related adverse effects. 
They will also be asked to complete the MMAS-8 questionnaire for adherence, the Treatment 
Satisfaction Questionnaire for Medication, and the Kansas City Cardiomyopathy Questionnaire for 
treatment-related quality of life among people with heart failure. As described above, participants 
will also complete telephone visits (weeks 2 and 6) to assess self-reported adherence and screen 
for adverse events.
Medical Record Review: We will review participants’ Epic-based medical records for comorbidities, 
medications, total daily pill burden, blood pressure, heart rate, and hospitalizations.
8.10  
: To what extent, if any, do the planned research procedures differ 
 STANDARD CLINICAL PRACTICE
*
from the care that people would otherwise receive at this institution or the study site if not being 
done locally: (REQUIRED)
 
The main difference from standard clinical practice is the over-encapsulation of GDMT into a 
single capsule, which will be a pharmacy-level packaging intervention (similar to a bubble pack). 
We hypothesize that this will reduce pill burden, improve treatment satisfaction, and improve 
adherence to heart failure therapies with proven mortality benefit. There are additional ways that 
this could impact care, which will be actively monitored by the pilot trial's investigators: 
Prior to randomization, participants who are not already prescribed guideline-directed 
quad therapy for HFrEF (beta blocker, SGLT2 inhibitor, MRA, and ACE/ARB/ARNI) will be 
initiated on these therapies at starting doses if no contraindications exist over the course 
of the first study visits. These therapies have proven mortality benefit in heart failure, and 
are part of guideline-directed care. Simultaneous or rapid-sequence initiation of these 
therapies with close monitoring is encouraged in expert consensus.
Thus, all participants 
11 
will be escalated to a guideline-directed HFrEF regimen prior to randomization, and in this 
way will undergo a form of intensified usual care.
More tablets may be cut in half in order to fit into a small capsule (for example, a half-tab 
of metoprolol succinate 100mg, rather than a whole tab of metoprolol succinate 50mg). 
This type of substitution is often performed at the pharmacy according to their formulary. 
Only pills that are explicitly allowed to be cut in half by the FDA would be split for the 
purposes of the study.
Like a bubble pack, this is primarily a packaging intervention, with individualization of 
patients' medication regimen and dosing. However, there may be some scenarios in which 
there is a minor medication change in order to accommodate the polypill intervention, if 
considered safe and clinically low-risk by the study clinician. These could include minor 
dose adjustments (for example, switching an SGLT2 inhibitor from 10mg daily to 12.5mg 
daily, if required by capsule size and covered by the patient's insurance; switching from 
metoprolol to comparable doses of a similar drug, bisoprolol, which has smaller pill size 
and is more amenable to the polypill intervention; or converting from twice-daily carvedilol 
to once-daily carvedilol extended release). At time of study consent, we will ask 
participants for permission to make small medication or dose adjustments for the 
purposes of the polypill intervention, with close monitoring and notification of their 
primary outpatient team. From our clinical experience, these adjustments have low risk of 
harm. Furthermore, participants will be monitored with at least monthly visits, which is 
more frequent than the typical standard of care, in addition to regular lab monitoring. This 
potential change and associated risks will be explained to participants as part of the 
informed consent process.
The follow-up schedule also differs from usual care, in that participants will be seen at least once 
a month for the duration of the study. As described above, participants will attend monthly follow-
up visits, which is at the upper limit of normal for heart failure management (in clinical care, 
patients are usually seen every 2-6 weeks while GDMT is being titrated, and then every 3-6 
months once they are on stable doses). At these visits, standard vital signs (heart rate, blood 
pressure, and oxygen saturation) and standing weight will be monitored, and patients will be 
screened for heart failure symptoms and medication side effects, as is routine for a cardiology 
clinic visit. Participants will also undergo regular lab monitoring, including a basic metabolic panel, 
as clinically indicated or at least every 2 months. This is a typical interval for patients whose 
GDMT is being actively titrated, but is more frequent than standard clinical are for patients on 
stable doses of GDMT (typical lab monitoring every 3-6 months).
8.11  
List all questionnaires, surveys, interview, or focus group guides that will be used 
INSTRUMENTS: 
* 

for this study: (REQUIRED)
Surveys:
MMAS-8 Questionnaire (published and validated)
Treatment Satisfaction Questionnaire for Medication (published and validated)
Kansas City Cardiomyopathy Questionnaire (published and validated)
Patients will be asked to self-report adherence to their medications, using a survey 
adapted from the Basic Medications Questionnaire (see Self-Reported Adherence 
Questionnaire as an attachment) 
Exit interviews: 
Health professional interview guide
Patient interview guide 
Community pharmacy partner interview guide
Attach any unpublished instruments in the 'Other Study Documents' 
section of the Initial Review Submission Packet form after 
completing the study application. Published instruments should 
NOT be attached.
8.12  
Are you drawing any blood or collecting other biosamples (e.g. tissue, 
* BIOSPECIMEN COLLECTION: 
buccal swabs, urine, saliva, hair, etc.) for analysis under this protocol and/or storage for future 
research: (REQUIRED)
 Yes  
 No
Could this study generate genetic data that may be broadly shared (e.g., submitted to 
* 
NIH in compliance with Genomic Data Sharing (GDS)/Genome-Wide Association 
 requirements): 
Studies (GWAS)
(REQUIRED)
  Yes  
  No
Based on current research trends, we strongly recommend 
including the 
 in the consent form to 
genomic data sharing language
allow future sharing, even if you don't anticipate it now. It's easier 
to add it now than trying to reconsent all the specimen donors!
8.13  
Briefly summarize the methods and types of analyses that will be 
 STATISTICAL METHODS: 
*
performed: (REQUIRED)
Quantitative outcomes: 
Demographic data for participants will be described in each group and compared using a Student’
s T-test (continuous variables) or Fisher’s exact test (categorical variables). We will use mixed 
model multilevel linear regression analyses to determine the effect of a polypill vs. usual care on 
the primary outcome (GDMT adherence) and secondary outcomes (including adherence ratio to 
ART, self-report of GDMT and other medication adherence using the MMAS-8 questionnaire, 
treatment satisfaction using the Treatment Satisfaction Questionnaire for Medication, and 
documented episodes of adverse effects related to GDMT use). We will report descriptive data 
pertaining to feasibility metrics, including production time and costs for polypill 
packaging.  Analyses will be performed according to an intention-to-treat principle, using Stata, 
version 17. The threshold for statistical significance will be P < 0.05. 
Qualitative outcomes (exit interviews): 
We will deploy a Framework Analysis approach to analyze our data. Members of the research 
team will read the transcripts several times to familiarize themselves with the text. Transcripts 
will be analyzed using deductive and inductive content analysis simultaneously. Members of the 
research team will develop a codebook after reviewing the transcripts. The resulting codebook will 
include codes reflecting topics from the interview guide, in addition to previously unexpected 

topics identified inductively. The draft coding scheme will be reviewed by the study team and 
reconciled by consensus. When the codebook is finalized, members of the research team will 
organize participants’ responses by the corresponding codes with support and guidance from co-
investigators. Common themes will be developed inductively, synthesizing participants’ responses 
across codes to reflect the themes. Coded transcript data will be charted into a framework matrix 
to facilitate the identification of themes around GDMT adherence and the pilot trial of an over-
encapsulated HFrEF polypill. The study team will then present these themes to the in-depth 
interview participants to confirm they represent the participant’s perspectives (member checking).
8.14  
List only the 5-10 most relevant references (a separate bibliography can be attached 
 REFERENCES: 
*
 
for reference purposes if this study involves novel approaches, agents, or an emerging technology 
that the IRB may not be familiar with): (REQUIRED)
1. Mohd Salleh NA, Richardson L, Kerr T, et al. A Longitudinal Analysis of Daily Pill Burden and 
Likelihood of Optimal Adherence to Antiretroviral Therapy Among People Living With HIV Who Use 
Drugs. 
. 2018;12(4):308-314. doi:10.1097/ADM.0000000000000403
J Addict Med
2. Krentz HB, Cosman I, Lee K, Ming JM, Gill MJ. Pill Burden in HIV Infection: 20 Years of 
Experience. 
. 2012;17(5):833-840. doi:10.3851/IMP2076
Antivir Ther
3. Tan JY, Greene M, Blat C, et al. Examining the Impact of the Golden Compass Clinical Care 
Program for Older People with HIV: A Qualitative Study. 
. 2022;26(5):1562-1571. doi:
AIDS Behav
10.1007/s10461-021-03509-0
4. Alvi RM, Afshar M, Neilan AM, et al. Heart failure and adverse heart failure outcomes among 
persons living with HIV in a US tertiary medical center. 
. 2019;210:39-48. doi:10.1016
Am Heart J
/j.ahj.2019.01.002
5. Greene SJ, Khan MS. Quadruple Medical Therapy for Heart Failure. 
. 2021;77
J Am Coll Cardiol
(11):1408-1411. doi:10.1016/j.jacc.2021.02.006
6. Bassi NS, Ziaeian B, Yancy CW, Fonarow GC. Association of Optimal Implementation of Sodium-
Glucose Cotransporter 2 Inhibitor Therapy With Outcome for Patients With Heart Failure. JAMA 
. 2020;5(8):948-951. doi:10.1001/jamacardio.2020.0898
Cardiol
7. Muñoz D, Uzoije P, Reynolds C, et al. Polypill for Cardiovascular Disease Prevention in an 
Underserved Population. 
. 2019;381(12):1114-1123. doi:10.1056/NEJMoa1815359
N Engl J Med
8. Castellano JM, Pocock SJ, Bhatt DL, et al. Polypill Strategy in Secondary Cardiovascular 
Prevention. 
. 2022;387(11):967-977. doi:10.1056/NEJMoa2208275
N Engl J Med
9. Pandey, A. Polypill Strategy for Heart Failure With Reduced Ejection Fraction. Clinical Trial 
Identifier: NCT04633005. Available at https://www.clinicaltrials.gov/ct2/show/NCT04633005.
10. Castellano JM, Sanz G, Peñalvo JL, et al. A Polypill Strategy to Improve Adherence: Results 
From the FOCUS Project. 
. 2014;64(20):2071-2082. doi:10.1016/j.jacc.
J Am Coll Cardiol
2014.08.021
11. Greene SJ, Butler J, Fonarow GC. Simultaneous or rapid sequence initiation of quadruple 
medical therapy for heart failure—optimizing therapy with the need for speed. JAMA cardiology. 
2021 Jul 1;6(7):743-4. 
9.0
 Biospecimen Collection and/or Bank Administration
9.1  
(check all that apply): 
TYPE OF SPECIMENS 
* 
(REQUIRED)
Blood (provide amount below)
Tissue (describe below)
Other type of biospecimen, such as sputum, cerebrospinal fluid, buccal swabs, etc. (describe 
below)
Existing/archival materials (name source below)
Briefly describe the types of biospecimens that will be collected. Provide the 
amount of blood, if applicable. For leftover/existing/archival material, 
identify the source:
A basic metabolic panel will be collected when determined by the study team to be clinically 
indicated, or at least once every 4 weeks. At these visits, less than 10cc of blood will be collected. 
We will also measure either a BNP or NT-ProBNP as an exploratory clinical outcome at baseline, 4 
weeks, and 8 weeks. Assuming a maximum of 5 blood collections per patent (weeks 0, 2, 4, 6, 
8), less than 50cc of blood total will be collected over the course of the study.

9.3  
(check all that apply): 
SPECIMENS ARE: 
* 
(REQUIRED)
Leftover specimens from a clinical diagnostic or therapeutic procedure
Specimens collected for research purposes only (including extra samples taken during a 
clinical procedure)
Other
9.5  
 
: Will any specimens or portions of specimens be retained after the study is 
* FUTURE SPECIMEN USE
over for possible use in future research studies: (REQUIRED)
  Yes  
  No
9.7  
Indicate where specimens will ultimately be stored: 
 SPECIMEN DESTINATION: 
*
(REQUIRED)
Indicate where specimens will be sent if they will not 
Outside Entities: 
remain at UCSF (choose at least one; check all that apply):
Cooperative group bank
NIH
Other university or collaborator
Industry sponsor
Other
N/A - all specimens will remain at UCSF
Specify to what institution, cooperative group, or company specimens will 
be transferred:
NT-ProBNP is a sendout test at ZSFG, performed by ARUP laboratories.
: If specimens will remain at UCSF, in what kind of 
Internal Storage
facility will they reside (choose at least one; check all that apply):
UCSF repository/bank being established under this protocol
Existing UCSF specimen repository/bank with IRB approval
National cooperative group bank housed at UCSF
Other location at UCSF (please describe)
N/A - no specimens will be retained at UCSF facilities
Please provide the name of the department, the program, and the physical 
location where the specimens will be housed. If the specimens will be 
stored in an already established bank, provide the name of the bank and its 
iRIS approval number.:
Samples will be collected at ZSFG in either the clinical laboratory or the research laboratory at 
5B. If needed, study samples will be transported by the study team from 5B to the clinical lab for 
processing, and/or securely stored prior to being sent to ARUP laboratories for processing of NT-
ProBNP.
9.8  
Will direct identifiers be associated with 
SPECIMENS SENT OUTSIDE UCSF - IDENTIFIABILITY: 
specimens or shared with other researchers and/or outside entities:
Yes 
No 
N/A - Specimens will not be shared with others 

If 
, which identifiers will be sent with specimens:
Yes
Name
Date of birth
Specimen collection dates
Social Security number
Medical record number
Address
Phone number
Email address
Other dates (surgery date, clinic visit dates, etc.)
Provide a justification for sending direct identifiers with the specimens:
ARUP laboratories is a partner of ZSFG and processes all NT-ProBNP samples for the hospital. If 
needed, we will send NT-ProBNP samples to ARUP laboratories in accordance with ZSFG 
procedures established by the clinical laboratory and research laboratory (5B). 
9.9  
Will clinical follow-up data be linked to specimens (i.e., will medical 
CLINICAL FOLLOW-UP DATA: 
* 
record information continue to be abstracted after the specimen is collected): (REQUIRED)
 Yes  
 No
Provide duration of follow-up or 'indefinitely':
The duration of the pilot trial period (approximately 2 months)
9.10  
UCSF-BANKED SPECIMENS - LINKING AND SHARING OF IDENTIFIERS: 
* 
(REQUIRED)
Samples are completely de-identified before being added to the bank/repository. There is no 
way to link the specimens back to the subjects.
Samples are coded and researchers are able to link the specimens to specific subjects.
Samples are stored with direct identifiers in the repository.
Explain under what circumstances identifiers may be released with 
specimens or say 'None' if identifiers will NEVER be released with 
specimens:
We will coordinate with the ZSFG clinical and research laboratory in order to process research 
specimens (i.e., basic metabolic panel or BNP). We will request that laboratory results are 
uploaded to ZSFG Epic if possible, since these results are clinically useful in the management of 
patients with HFrEF. We may securely store samples with identifiers (name, MRN, DOB) prior to 
sending samples to ARUP laboratories for sendout tests, i.e. NT-ProBNP.
9.11  
–
 List the identifiers that will be collected, stored, or 
UCSF-BANKED SPECIMENS  IDENTIFIERS:
linked with the specimens:
Name
Date of birth
Social Security number
Medical record number
Address
Phone number
Email address
Other dates (dates of surgery, visit dates)
9.12  
Specimens banked at UCSF may be made available to (check all that apply):
DISTRIBUTION: 

UCSF researchers
Non-UCSF researchers
Industry
None of the above - specimens will be retained and used within our own research program
9.13  
Is there a formal utilization review process for distribution of specimens:
UTILIZATION REVIEW: 
 Yes  
 No
Describe the process:
Our study participants will be getting some labs that are part of routine clinical care (e.g. 
checking a metabolic panel after starting a guideline-directed heart failure medication). These 
labs will be billed to insurance through the standard clinical laboratory. The participants will also 
get some labs solely for the purpose of the study (e.g. baseline lab tests prior to the 
intervention); these will be paid for by the study. This will be managed in accordance with ZSFG 
research laboratory processes, by either 1) collecting the specimens at the 5B research laboratory 
or 2) using the standard clinical laboratory and billing the study instead of insurance. We will 
work with the ZSFG clinical research service to adhere to all relevant processes and procedures.
10.0
 Drugs and Devices
10.1  
Are you 
 any drugs and/or biologics that are either 
* DRUGS AND/OR BIOLOGICS: 
STUDYING
approved or unapproved: (REQUIRED)
 Yes  
 No
If you have questions about FDA requirements for drug or device 
research, you can send an 
to request a consult.
email 
10.2  
List the drugs or biologics that will be studied. In the drug details 
LIST THE DRUGS OR BIOLOGICS: 
screen you will be asked questions such as: 
Whether the drug or biologic is FDA approved
If the drug or biologic will be provided at no cost
If an IND is necessary, the IND number, and who holds the IND
If the drug or biologic is FDA approved and an IND is not required, the rationale for the 
decision
If the 
 
 is dispensing the drug or biologic (required unless a 
Investigational Drug Service (IDS)
 is obtained from the IDS)
waiver
Please see the 
 for more details about the use of drugs and biologics in research, 
UCSF IRB website
  
including the 
.
IND Decision Worksheet  
 If the sponsor’s protocol does 
Verification of IND numbers:
not list the IND number, you must submit documentation from the sponsor or FDA identifying the 
IND number for this study. Attach this documentation in the Other Study Documents section of the 
  
Initial Review Submission Packet.  If you have any correspondence from the FDA or 
sponsor regarding this drug or biologic, please attach it to the application.
View 
Details
Drug Name
FDA Approved
A new drug or 
a new use of 
an already 
approved 
drug:
IND Number
Trade Drug 
Name: Jardiance
Generic Drug 
Name: empagliflozin
Investigational 
Drug Name:
Yes 
Yes 
 

Trade Drug Name:
Jardiance 
Generic Drug Name:
empagliflozin 
Investigational Drug Name:
Identify the name of the 
manufacturer or source of 
investigational drug/biologic:
Boehringer Ingelheim  
Is the drug supplied at no cost?
No  
Is the Drug FDA Approved:
Yes  
Is this a new drug or a new 
use of an already approved 
drug
Yes  
Is an IND necessary
No  
IND Number
Who holds the IND:
N/A  
IND details:
If FDA Approved and an IND is 
not required, Please provide a 
rationale for exemption:
The polypill will be a late-stage packaging intervention to 
reduce pill burden, without restricting dose possibilities or 
interfering with medication titration. All medications 
included will be used for FDA-approved indications at 
standard dosing. We are requesting that the UCSF IRB 
make an IND Exempt determination, and have attached the 
IND Decision worksheet. Our collaborator Dr. Mark Huffman 
similarly received an IND exempt determination for an over-
encapsulated polypill for hypertension (QUARTET-USA, 
NCT03640312).  
Are you currently using this 
IND in another research 
project?
No  
If yes, list the IRB Number(s):
Will the investigational 
pharmacy be dispensing?
No  
If the source is not a FDA 
licensed facility, provide details 
regarding the purity, quality, 
stability and sterility of the 
investigational drug/biologic:
Trade Drug 
Name: Dapagflozin
Generic Drug 
Name:
Investigational 
Drug Name:
Yes 
Yes 
Trade Drug Name:
Dapagflozin 
Generic Drug Name:
Investigational Drug Name:
Identify the name of the 
manufacturer or source of 
investigational drug/biologic:
AstraZeneca  
Is the drug supplied at no cost?
No  
Is the Drug FDA Approved:
Yes  
Is this a new drug or a new 
use of an already approved 
drug
Yes  

Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
If FDA Approved and an IND is 
not required, Please provide a 
rationale for exemption:
Please see above  
Are you currently using this 
IND in another research 
project?
No  
If yes, list the IRB Number(s):
 
Will the investigational 
pharmacy be dispensing?
No  
If the source is not a FDA 
licensed facility, provide details 
regarding the purity, quality, 
stability and sterility of the 
investigational drug/biologic:
 
Trade Drug 
Name:
METOPROLOL 
SUCCINATE
Generic Drug 
Name:
METOPROLOL 
SUCCINATE
Investigational 
Drug Name:
Yes 
Yes 
 
Trade Drug Name:
METOPROLOL SUCCINATE 
Generic Drug Name:
METOPROLOL SUCCINATE 
Investigational Drug Name:
 
Identify the name of the 
manufacturer or source of 
investigational drug/biologic:
Generic  
Is the drug supplied at no cost?
No  
Is the Drug FDA Approved:
Yes  
Is this a new drug or a new 
use of an already approved 
drug
Yes  
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
If FDA Approved and an IND is 
not required, Please provide a 
rationale for exemption:
Please see above  
Are you currently using this 
IND in another research 
project?
No  
If yes, list the IRB Number(s):
 
Will the investigational 
pharmacy be dispensing?
No  
If the source is not a FDA 
licensed facility, provide details 
regarding the purity, quality, 
stability and sterility of the 
investigational drug/biologic:
 

Trade Drug 
Name: SPIRONOLACTONE
Generic Drug 
Name: SPIRONOLACTONE
Investigational 
Drug Name:
Yes 
Yes 
 
Trade Drug Name:
SPIRONOLACTONE 
Generic Drug Name:
SPIRONOLACTONE 
Investigational Drug Name:
 
Identify the name of the 
manufacturer or source of 
investigational drug/biologic:
Generic  
Is the drug supplied at no cost?
No  
Is the Drug FDA Approved:
Yes  
Is this a new drug or a new 
use of an already approved 
drug
Yes  
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
If FDA Approved and an IND is 
not required, Please provide a 
rationale for exemption:
Please see above  
Are you currently using this 
IND in another research 
project?
No  
If yes, list the IRB Number(s):
 
Will the investigational 
pharmacy be dispensing?
No  
If the source is not a FDA 
licensed facility, provide details 
regarding the purity, quality, 
stability and sterility of the 
investigational drug/biologic:
 
Trade Drug 
Name: EPLERENONE
Generic Drug 
Name: EPLERENONE
Investigational 
Drug Name:
Yes 
Yes 
 
Trade Drug Name:
EPLERENONE 
Generic Drug Name:
EPLERENONE 
Investigational Drug Name:
 
Identify the name of the 
manufacturer or source of 
investigational drug/biologic:
Generic  
Is the drug supplied at no cost?
No  
Is the Drug FDA Approved:
Yes  
Is this a new drug or a new 
use of an already approved 
Yes  

drug
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
If FDA Approved and an IND is 
not required, Please provide a 
rationale for exemption:
Please see above  
Are you currently using this 
IND in another research 
project?
No  
If yes, list the IRB Number(s):
 
Will the investigational 
pharmacy be dispensing?
No  
If the source is not a FDA 
licensed facility, provide details 
regarding the purity, quality, 
stability and sterility of the 
investigational drug/biologic:
 
Trade Drug 
Name:
BISOPRODOL 
FUMARATE
Generic Drug 
Name:
BISOPROLOL 
FUMARATE
Investigational 
Drug Name:
Yes 
Yes 
 
Trade Drug Name:
BISOPRODOL FUMARATE 
Generic Drug Name:
BISOPROLOL FUMARATE 
Investigational Drug Name:
 
Identify the name of the 
manufacturer or source of 
investigational drug/biologic:
Generic  
Is the drug supplied at no cost?
No  
Is the Drug FDA Approved:
Yes  
Is this a new drug or a new 
use of an already approved 
drug
Yes  
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
If FDA Approved and an IND is 
not required, Please provide a 
rationale for exemption:
Please see above  
Are you currently using this 
IND in another research 
project?
No  
If yes, list the IRB Number(s):
 
Will the investigational 
pharmacy be dispensing?
No  
If the source is not a FDA 
licensed facility, provide details 
regarding the purity, quality, 
 

stability and sterility of the 
investigational drug/biologic:
Trade Drug 
Name: LISINOPRIL
Generic Drug 
Name: LISINOPRIL
Investigational 
Drug Name:
Yes 
Yes 
 
Trade Drug Name:
LISINOPRIL 
Generic Drug Name:
LISINOPRIL 
Investigational Drug Name:
 
Identify the name of the 
manufacturer or source of 
investigational drug/biologic:
Generic  
Is the drug supplied at no cost?
No  
Is the Drug FDA Approved:
Yes  
Is this a new drug or a new 
use of an already approved 
drug
Yes  
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
If FDA Approved and an IND is 
not required, Please provide a 
rationale for exemption:
See above  
Are you currently using this 
IND in another research 
project?
No  
If yes, list the IRB Number(s):
 
Will the investigational 
pharmacy be dispensing?
No  
If the source is not a FDA 
licensed facility, provide details 
regarding the purity, quality, 
stability and sterility of the 
investigational drug/biologic:
 
Trade Drug 
Name: LOSARTAN
Generic Drug 
Name:
LOSARTAN 
POTASSIUM
Investigational 
Drug Name:
Yes 
Yes 
 
Trade Drug Name:
LOSARTAN 
Generic Drug Name:
LOSARTAN POTASSIUM 
Investigational Drug Name:
 
Identify the name of the 
manufacturer or source of 
investigational drug/biologic:
Generic  
Is the drug supplied at no cost?
No  
Is the Drug FDA Approved:
Yes  

Is this a new drug or a new 
use of an already approved 
drug
Yes  
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
If FDA Approved and an IND is 
not required, Please provide a 
rationale for exemption:
See above  
Are you currently using this 
IND in another research 
project?
No  
If yes, list the IRB Number(s):
 
Will the investigational 
pharmacy be dispensing?
No  
If the source is not a FDA 
licensed facility, provide details 
regarding the purity, quality, 
stability and sterility of the 
investigational drug/biologic:
 
Trade Drug 
Name: VALSARTAN
Generic Drug 
Name: VALSARTAN
Investigational 
Drug Name:
Yes 
Yes 
 
Trade Drug Name:
VALSARTAN 
Generic Drug Name:
VALSARTAN 
Investigational Drug Name:
 
Identify the name of the 
manufacturer or source of 
investigational drug/biologic:
Generic  
Is the drug supplied at no cost?
No  
Is the Drug FDA Approved:
Yes  
Is this a new drug or a new 
use of an already approved 
drug
Yes  
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
If FDA Approved and an IND is 
not required, Please provide a 
rationale for exemption:
See above  
Are you currently using this 
IND in another research 
project?
No  
If yes, list the IRB Number(s):
 
Will the investigational 
pharmacy be dispensing?
No  
If the source is not a FDA 

licensed facility, provide details 
regarding the purity, quality, 
stability and sterility of the 
investigational drug/biologic:
 
Trade Drug 
Name: Entresto
Generic Drug 
Name:
sacubitril
/valsartan
Investigational 
Drug Name:
Yes 
No 
 
Trade Drug Name:
Entresto 
Generic Drug Name:
sacubitril/valsartan 
Investigational Drug Name:
 
Identify the name of the 
manufacturer or source of 
investigational drug/biologic:
Novartis  
Is the drug supplied at no cost?
No  
Is the Drug FDA Approved:
Yes  
Is this a new drug or a new 
use of an already approved 
drug
No  
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
If FDA Approved and an IND is 
not required, Please provide a 
rationale for exemption:
The polypill will be a late-stage packaging intervention to 
reduce pill burden, without restricting dose possibilities or 
interfering with medication titration. All medications 
included will be used for FDA-approved indications at 
standard dosing. We are requesting that the UCSF IRB 
make an IND Exempt determination, and have attached the 
IND Decision worksheet. Our collaborator Dr. Mark Huffman 
similarly received an IND exempt determination for an over-
encapsulated polypill for hypertension (QUARTET-USA, 
NCT03640312).  
Are you currently using this 
IND in another research 
project?
No  
If yes, list the IRB Number(s):
 
Will the investigational 
pharmacy be dispensing?
No  
If the source is not a FDA 
licensed facility, provide details 
regarding the purity, quality, 
stability and sterility of the 
investigational drug/biologic:
 
Trade Drug 
Name: COREG CR
Generic Drug 
Name:
CARVEDILOL 
PHOSPHATE
Investigational 
Drug Name:
Yes 
No 
 
Trade Drug Name:
COREG CR 
Generic Drug Name:
CARVEDILOL PHOSPHATE 

Investigational Drug Name:
 
Identify the name of the 
manufacturer or source of 
investigational drug/biologic:
Generic  
Is the drug supplied at no cost?
No  
Is the Drug FDA Approved:
Yes  
Is this a new drug or a new 
use of an already approved 
drug
No  
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
If FDA Approved and an IND is 
not required, Please provide a 
rationale for exemption:
The polypill will be a late-stage packaging intervention to 
reduce pill burden, without restricting dose possibilities or 
interfering with medication titration. All medications 
included will be used for FDA-approved indications at 
standard dosing. We are requesting that the UCSF IRB 
make an IND Exempt determination, and have attached the 
IND Decision worksheet. Our collaborator Dr. Mark Huffman 
similarly received an IND exempt determination for an over-
encapsulated polypill for hypertension (QUARTET-USA, 
NCT03640312).  
Are you currently using this 
IND in another research 
project?
No  
If yes, list the IRB Number(s):
 
Will the investigational 
pharmacy be dispensing?
No  
If the source is not a FDA 
licensed facility, provide details 
regarding the purity, quality, 
stability and sterility of the 
investigational drug/biologic:
 
Trade Drug 
Name: CARVEDILOL
Generic Drug 
Name: CARVEDILOL
Investigational 
Drug Name:
Yes 
Yes 
 
Trade Drug Name:
CARVEDILOL 
Generic Drug Name:
CARVEDILOL 
Investigational Drug Name:
 
Identify the name of the 
manufacturer or source of 
investigational drug/biologic:
Generic  
Is the drug supplied at no cost?
No  
Is the Drug FDA Approved:
Yes  
Is this a new drug or a new 
use of an already approved 
drug
Yes  
Is an IND necessary
No  
IND Number
 

Who holds the IND:
N/A  
IND details:
 
If FDA Approved and an IND is 
not required, Please provide a 
rationale for exemption:
IND determination was previously provided by the IRB for 
the use of an empty capsule to copackage several common 
heart failure medications. We are maintaining the accuracy 
of this list by adding carvedilol (the short acting version of 
Coreg CR). Other cardiovascular medications, not on this 
list, may be copackaged in the capsule if capsule size 
permits.  
Are you currently using this 
IND in another research 
project?
No  
If yes, list the IRB Number(s):
 
Will the investigational 
pharmacy be dispensing?
No  
If the source is not a FDA 
licensed facility, provide details 
regarding the purity, quality, 
stability and sterility of the 
investigational drug/biologic:
 
10.3  
: Are you 
 any medical devices, in vitro diagnostics, or assays that are 
* MEDICAL DEVICES
STUDYING
 
either approved or unapproved:(REQUIRED)
  Yes  
  No
If you have questions about FDA requirements for drug or device 
research, you can send an email to request a consult.
10.6  
Is this an expanded access or compassionate use protocol, meaning the 
* EXPANDED ACCESS: 
primary purpose is to diagnose, monitor or treat a patient's condition, rather than the collection of 
safety and efficacy data of the experimental agent: (REQUIRED)
  Yes  
  No
11.0
 Sample Size and Eligibility Criteria
11.1  
How many people will you enroll: 
ENROLLMENT TARGET: 
* 
(REQUIRED)
51
 If there are multiple participant groups, indicate how many people will be 
in each group:
PATIENTS: n = 20-40 
In this crossover trial, participants will be randomized in 1:1 fashion into the AB group (polypill 
followed by usual care), or the BA group (usual care followed by polypill). Given that this is a 
small pilot feasibility study, actual sample size will be modified in accordance with actual logistical 
constraints.
CLINICIANS: n = 4-8
We will conduct exit interviews with nurses (n = 1-2), pharmacists (n = 1-2), and ZSFG 
prescribers (n = 2-4) to discuss their observations of the intervention. 
DANIEL'S PHARMACY STAFF: n = 3
We will observe pharmacy technicians and clinical pharmacists (n = 2-3) at our community 
partner, Daniel's Pharmacy, in order to collect feasibility metrics, i.e., time and cost of producing 

the polypill. We will also conduct exit interviews with these community pharmacy partners (n = 2-
3) to discuss their experience with the polypill intervention.
11.3  
Explain how and why the number of people was chosen. For multi-
SAMPLE SIZE JUSTIFICATION: 
*
site studies, this is referring to the number that will be enrolled across all sites: (REQUIRED)
In the FOCUS trial of an over-encapsulated polypill for hypertension, patients randomized to a 
polypill were 24% more likely to be adherent compared to those receiving separate pills (50.8% 
adherence in polypill group vs. 41% adherence in usual care, p = 0.019; OR, 1.24; 95% CI, 1.06-
1.47).
 Considering a power of 80% and alpha of 5%, using a two-treatment crossover trial 
10
design, a minimum sample size of 20 participants total (10 per arm) will be necessary to identify 
a 20% absolute change in adherence ratio among patients prescribed the polypill vs. usual care, 
assuming a standard deviation of 30% in the change in adherence ratio over time. Assuming that 
up to 50% of patients will not complete the run-in period, we estimate that 40 patients (20 per 
arm) should be recruited. However, as described above, this is primarily a feasibility pilot study 
and the sample size may be modified in response to logistical constraints.
For the exit interviews with healthcare professionals, we will recruit approximately 4-8 HCPs at 
ZSFG (nurses, pharmacists, and prescribers) as well as approximately 2-3 community 
pharmacists or pharmacy technicians at Daniel's Pharmacy. If theoretical saturation is not 
reached, additional HCPs who interfaced with the intervention can be recruited for exit interviews. 
11.4  
Eligible age ranges: 
*
 AGE RANGE: 
PARTICIPANT
(REQUIRED)
0-6 years
7-12 years
13-17 years
18-64 years
65+
11.5  
 Data will be collected from or about the following types of people (check all
STUDY POPULATIONS:
*
that apply): (REQUIRED)
Inpatients
Outpatients
Family members or caregivers
Providers
People who have a condition but who are not being seen as patients
Healthy volunteers
Students
Staff of UCSF or affiliated institutions
None of the above
11.6  
Check the populations that may be enrolled: 
SPECIAL SUBJECT GROUPS: 
*
(REQUIRED)
Children / Minors
Adult subjects unable to consent for themselves
Adult subjects unable to consent for themselves (emergency setting)
Subjects with diminished capacity to consent
Subjects unable to read, speak or understand English
Pregnant women
Fetuses
Neonates
Prisoners
Economically or educationally disadvantaged persons
None of the above

If not already addressed in the Background and Significance questions in 
the Research Plan section or elsewhere, explain why it is appropriate to 
include the types of subjects checked above in this particular study:
Our study is based at ZSFG, which serves an economically disadvantaged patient population. This 
is also the population that we hope would benefit most from a combination pill for heart failure, 
since patients who are economically or socially disadvantaged face higher barriers to adherence 
to a complex, 4-drug regimen. Our study will also focus on a specific population of patients with 
HIV and HFrEF, who have high pill burden and face unique barriers to medication adherence. 
Single-pill combination therapies for HIV greatly expanded access to ART in this population; 
however, there are no combination therapies available for most cardiac conditions, which now 
comprise a majority of pill burden for many PWH at ZSFG.
Describe the additional safeguards that have been included in the study to 
protect the rights and welfare of these subjects and minimize coercion or 
undue influence:
Here are some examples:
evaluating capacity to consent for individuals who may be decisionally 
impaired (specify how)
calibrating payment amounts to be non-coercive for the financially 
disadvantaged
conducting more in-depth evaluations of subjects’ understanding of 
the study and the voluntary nature of participation
involving advocates in the consent process
More information and other safeguards are described here: Vulnerable 
 and 
.
Subject Populations
Recruiting Staff and Students
After reviewing patient eligibility, patients will be given an overview of the study by a coordinator 
or other study team member. All questions will be answered to his/her satisfaction prior to 
providing verbal consent for participation. To minimize coercion, the research team will make 
sure the patients know the study is voluntary and choosing to participate or not will not affect 
their care. If the patient agrees to participate, the coordinator will arrange a time to schedule the 
interview.
11.7  
 Briefly describe the population(s) that will be involved in this study.
INCLUSION CRITERIA: 
*
Include anyone that data will be collected from or about (e.g. patients, healthy controls, caregivers,
providers, administrators, students, parents, family members, etc.): (REQUIRED)
PATIENT PARTICIPANTS:
Age 
 18 years old
>
Previously diagnosed with heart failure with reduced ejection fraction ( 
0% on most 
<5
recent echocardiogram or cardiac MRI), ACCF/AHA stage C or D, NYHA class II-IV
With or without a prior diagnosis of HIV (HIV+ and HIV- subgroups)
Able to conveniently obtain medications  through one of 3 available mechanisms (mail, 
pick up at a ZSFG clinic, or pick up at Daniel’s pharmacy)
Last eGFR > 30 
Working telephone number for telephone follow-up 
CLINICIANS RECRUITED FOR EXIT INTERVIEWS:
Nurses, pharmacists, patient care navigators, or prescribers who work at ZSFG in the 
Ward 86 or cardiology clinics
Observed or interfaced with the polypill trial at ZSFG
DANIEL'S PHARMACY STAFF: 

Pharmacy technicians or clinical pharmacists employed at Daniel's Pharmacy, who have 
direct participation in polypill preparation and packaging
11.8  
 List any exclusion criteria (e.g. reasons why someone would not be
EXCLUSION CRITERIA:
*
included in the study): (REQUIRED)
PATIENTS:
Patients who are not fluent in English. These patients are excluded from this small pilot 
trial for feasibility reasons (e.g. access to medical interpreters for the consent process and 
exit interviews), however, we plan to include these patients in a larger subsequent trial. 
Patients who have dementia or lack capacity
Patients who are incarcerated
Patients who cannot provide informed consent
Patients with a ventricular assist device (VAD) or patients with an MI, unstable angina, 
stroke, or TIA within 12 weeks prior to enrollment
Women who are pregnant, breastfeeding or of childbearing potential and are not using and 
do not plan to continue using medically acceptable form of contraception throughout the 
study (pharmacological or barrier methods). 
Concomitant medical condition which in the opinion of the study team could interfere with 
the safe conduct of the study including outcome assessment. 
Participation in a concurrent interventional medical investigation or pharmacologic clinical 
trial. Patients in observational, natural history or epidemiological studies not involving an 
intervention are eligible. 
Participant’s responsible physician believes it is not appropriate for participant to take part 
in the study.
Unable to complete study procedures and/or plan to move out of the study area in the 
next 2 months.
CLINICIANS:
Clinicians who are co-investigators on the proposed study
Those who have not cared for patients enrolled in the polypill trial, or otherwise interfaced 
with the polypill intervention at ZSFG
DANIEL'S PHARMACY STAFF: 
Those who have not had hands-on experience with polypill packaging and preparation
11.9  
Do any study activities take place on any
* RESEARCH CONDUCTED ON PATIENT CARE WARDS: 
patient care units including inpatient wards, peri- or post-operative care units, operating rooms, or
in the Emergency Department at UCSF Health medical facilities: (REQUIRED)
  Yes  
  No
11.11  
Does your protocol or study involve any of the following patient
EMERGENCY DEPARTMENT: 
*
related activities in the emergency department (e.g. subject identification, recruitment, consent,
blood draws, specimen retrieval, involvement of ED staff (nursing, tech, and/or physician), or any
other ED based procedures): (REQUIRED)
  Yes  
  No
12.0
Recruitment and Consent
12.1  
Is this a competitive enrollment clinical trial? By competitive
* COMPETITIVE ENROLLMENT: 
enrollment, we mean that sites who do not enroll participants early may not get to participate at all:
(REQUIRED)

  Yes  
  No
12.2  
What kinds of methods will be used to identify potential
* SUBJECT IDENTIFICATION METHODS: 
participants for recruitment (check all that apply): (REQUIRED)
Review of patients' conditions, history, test results, etc. (includes patients seen in clinic, 
scheduled for surgery, a procedure, imaging, or tests, or seen in the Emergency Department 
as well as searching through medical record data for possible cohort identification)
Already approved recruitment registry
Re-contact of participants from the investigators' previous studies
Referrals from colleagues (attach the 'Dear Colleague' letter or other recruitment materials 
you will provide to colleagues)
Referrals from the community / word of mouth
Advertisements (flyers, brochures, radio or t.v. ads, posting on clinical research sites or social 
media, presentation of the study at community events/media, etc.)
Online recruiting tool (describe below)
CTSI Recruitment Services unit
Posting on UCSF Clinical Trials, ClinicalTrials.gov or other publicly available clinical trial website
Other method (describe below)
* Provide details about the subject identification methods: (REQUIRED)
Patients will be identified as potential study candidates by the investigator, co-investigator or 
research coordinator through one of the following mechanisms: 
1) Prior studies: Patients from a prior qualitative study (IRB # 22-38189) who expressed interest
in a HFrEF polypill pilot trial and consented to further contact will be asked if they would like to
participate.
2) Clinical lists, with approval from a DPH clinician: The research team will identify potential
participants using existing clinical lists within our divisions (the Epic Heart Failure registry, the
cardiology and Ward 86 clinic lists, and the cardiology and family medicine inpatient lists). The
ZSFG heart failure registry is a clinical tool within Epic that was co-developed by Dr. Jonathan
Davis (co-investigator on the present study) and is used for heart failure panel management and
quality improvement at ZSFG. Recruitment through the ZSFG heart failure registry will allow us to
identify potential participants who are not currently connected to the cardiology clinic, and thus,
may serve to benefit more from medication titration using a polypill strategy. DPH clinicians (i.e.
cardiovascular clinical pharmacist Christina Wang) will pre-approve the use of Epic reports or Epic
lists, such as the HFrEF registry list, prior to contacting participants for recruitment for the study.
Customized columns in Epic lists and data fields in Epic reports (for example, age, renal function,
HIV status, contact information) will be used to screen potentially eligible participants without
opening their chart. In some cases, researchers may want to open the patient's chart to review
their eligibility prior to contacting the patient for recruitment & consent. In these cases,
researchers will get approval from the patient or from the patient's own healthcare provider prior
to opening their chart to screen for study eligibility.
3) Provider referrals: we will present at providers' meetings and request referrals from ZSFG
clinicians in cardiology, general medicine and Ward 86.
4) Fliers: if needed to meet recruitment goals, we will post study fliers in patient waiting rooms,
specifically in the Ward 86 and/or cardiology outpatient areas. See attached flier draft.
Clinicians and Daniel's Pharmacy staff will be identified as candidates for exit interviews by a 
member of the research team. Lists or groups of clinicians will be approved by a DPH clinician 
prior to contact for study recruitment. As described in the inclusion criteria, we will recruit 
clinicians and Daniel's Pharmacy staff who interfaced with the polypill intervention for exit 
interviews to learn more about their experience with the polypill. We will also observe some 
members of Daniel's Pharmacy staff preparing the polypill in order to gather feasibility metrics 
(time and cost of production).
Did all the participants of previous studies provide permission to be
*
contacted for future studies: (REQUIRED)

 Yes  
 No
12.3  * SEARCHING OF MEDICAL RECORDS: (REQUIRED)
Whose patients are they:
Investigators' own patients or patients seen within the same practice
Patients not under the care of the investigators
How and by whom will records be accessed and searched (check all that 
apply):
Self-search in APeX or other medical records source
Self-search using UCSF's Research Cohort Selection Tool
CTSI Consultation Service Recruitment Services
UCSF Academic Research Services (ARS)
University of California Research Exchange (UC ReX)
Other method (describe below)
12.4  
How, when, and by whom will eligibility for recruitment be
DETERMINATION OF ELIGIBILITY: 
*
determined: (REQUIRED)
As described above, the research team will identify potential participants from provider referrals, 
patient self-referrals, prior study participants who agreed to future contact, or existing clinical 
lists within our divisions (the Epic Heart Failure registry, the cardiology and Ward 86 clinic lists, 
and the cardiology and family medicine inpatient lists). The ZSFG heart failure registry is a clinical 
tool within Epic that was co-developed by Dr. Jonathan Davis (co-investigator on the present 
study) and is used for heart failure panel management and quality improvement at ZSFG. 
Recruitment through the ZSFG heart failure registry will allow us to identify potential participants 
who are not currently connected to the cardiology clinic, and thus, may serve to benefit more 
from medication titration using a polypill strategy. DPH clinicians (i.e. cardiovascular clinical 
pharmacist Christina Wang) will pre-approve the use of Epic reports or Epic lists, such as the 
HFrEF registry list, prior to contacting participants for recruitment for the study. Customized 
columns in Epic lists and data fields in Epic reports (for example, age, renal function, HIV status, 
contact information) will be used to screen potentially eligible participants without opening their 
full chart. In some cases, researchers may want to open the patient's chart to review their 
eligibility prior to contacting the patient for recruitment & consent. In these cases, researchers 
will get approval from the patient or from the patient's own healthcare provider prior to opening 
their chart to screen for study eligibility.
As part of the initial recruitment call, the study team may ask some pre-screening questions to 
determine if the patient meets inclusion criteria prior to arranging an in-person visit. If this 
information is already known from a referring clinician or from Epic lists, these pre-screening 
questions may be skipped. These questions pertain to pill-taking practices (e.g. use of a pill box 
or MediSet) and do not include any questions about diagnoses or medical history. These pre-
screening questions are listed below and also in the revised telephone script: 
"In order to see if you might be eligible for this study, can I ask you a few screening 
questions? 
Do you currently use a bubble pack or pillbox? 
Does anyone help you with your medications? 
Out of the past week, how many days do you think you took all of your medications? Have 
you ever had difficulty taking all of your medications? 
If patient does not meet criteria: 
Based on this information, this study is not quite right for you, but hopefully there will be another 
study in the future that is a better fit. Thank you so much for your time today. Have a good day!"
Specifically, participants would be excluded from the study if they use a bubble pack or if they 
have someone who helps administer all of their medications. Potential participants who report 

perfect adherence will be excluded from initial recruitment efforts, given that we are preferentially 
recruiting those who miss some doses of their medication; however, they may be included at a 
later time depending on recruitment targets.
Daniel's Pharmacy staff will be approached for recruitment in exit interviews if they were involved 
in manufacturing the polypill. ZSFG clinicians will be contacted for exit interviews if they cared for 
patients receiving the polypill intervention. A DPH clinician will approve groups of possible HCP 
participants prior to contacting them.
12.5  
Who initiates contact (check all that apply): 
INITIATION OF CONTACT: 
*
(REQUIRED)
Investigators/study team
UCSF recruitment unit (e.g. CTSI Consultation Services)
Potential participant
Other (explain below)
12.6  
 (check all that apply): 
HOW IS CONTACT INITIATED:
*
(REQUIRED)
In person
Phone
Letter / email
Website or app
Other (explain below)
Attach the telephone recruitment script in the Other Study 
Documents section of the Initial Review Submission Packet Form. If 
potential participants will initiate contact, attach the telephone 
screening script that will be used to provide more information about 
the study and determine if callers are eligible to participate.
Attach the recruitment letter or email template in the Other Study 
Documents section of the Initial Review Submission Packet Form.
12.7  
Based on the checkboxes you chose above, please provide a narrative 
RECRUITMENT PLAN: 
describing your recruitment plan. We want to know:
Who is conducting the search for potential participants, and how?
How are potential subjects being approached for recruitment? By whom, and when?
If there will be more than one participant group (e.g. patients, healthy controls, caregivers, family 
members, providers, etc.), provide details about the recruitment plans for each group. 
(Recommended length - 100-250 words)
After reviewing patient eligibility with the PI or co-PI, and in accordance with the processes 
described above, contact with patients will be initiated by a trained study investigator or staff 
member. Contact will be initiated in-person or by telephone. 
The patient will be given an overview of the study by a coordinator or other study team member. 
All questions will be answered to his/her satisfaction prior to providing written consent for 
participation. To minimize coercion, the research team will make sure the patients know the study 
is voluntary and choosing to participate or not will not affect their care. If the patient agrees to 
participate, the coordinator will arrange a time to schedule an intake visit. The process to recruit 
participants will be led and coordinated by trained study team members.
Contact with Daniel's Pharmacy staff members will be initiated in-person. Contact with ZSFG 
clinicians will be initiated in-person or by email; please see the attached ZSFG clinician email 
recruitment script.
12.8  
How will permission to participate (i.e., informed consent) be obtained from 
CONSENT METHODS: 
* 

each potential participant. If there will be multiple groups and different plans for consenting each, 
  
check all that apply. See the orange Help bubble to the right for more detailed guidance.  
 
Participants will (check all that apply): (REQUIRED)
Sign a paper consent form at the end of the consent discussion (signed consent)
Sign an electronic consent form using DocuSign or REDCap’s e-signature function (signed 
consent)
Provide online unsigned consent through an app, a website, or a survey tool such as Qualtrics 
or REDCap (waiver of signed consent)
Be told about the study and be given a handout/information sheet and be asked if they agree 
to participate (verbal consent - waiver of signed consent)
Complete the study activities and turn in materials, as in the case of a completed survey that 
is placed in a drop box or mailed to the study team (implied consent - waiver of signed 
consent)
Not be able to provide consent and will have a family member consent for them, as in the 
case of a critically ill or unconscious patient (surrogate consent)
Not able to provide consent (emergency medicine, greater than minimal risk waiver/alteration 
of consent - requires an approved community consultation plan)
Not able to provide consent (emergency medicine, minimal risk waiver/alteration of consent)
Not know about the study, as in the case of chart reviews or observations of public behavior 
(waiver of consent)
Other method (describe below)
Attach your consent form, information sheet, or electronic consent 
text in the Informed Consent Documents section of the Initial 
Review Submission Packet Form.
If this study is FDA-regulated (i.e., involves investigational drugs or 
devices, or approved drugs or devices for investigational uses) and 
you want to use DocuSign or REDCap to collect research signatures, 
you must use an FDA-compliant version of DocuSign or REDCap. 
More information is available at FAQ #2. For the FDA-compliant 
version of DocuSign, submit an access request at https://ucsf.
service-now.com/ucsfit and contact it-cloudapps@ucsf.edu with 
questions. For the FDA-compliant version of REDCap (“REDCap 
Premium”), go to https://redcap-prem.ucsf.edu and contact 
Academic Research Systems Support with questions.
12.9  
Describe the process for obtaining informed consent, including details such as
CONSENT PROCESS: 
*
who will have the consent discussion and when participants will be asked to sign the consent form in
relation to finding out about the study: (REQUIRED)   We encourage researchers to review our
.
guidance on obtaining and documenting informed consent
If there are multiple groups being consented differently, provide details about the consent 
process for each group.
If you are relying on 
, provide details about how that will happen.
verbal or implied consent
For studies using online recruitment and consent or consent via mail, provide details here.
We will obtain informed consent from participants prior to their participation in the pilot trial using 
paper, Docusign or Redcap. Please see the attached consent documents. As part of the consent 
process, potential participants will be provided a description of the study, including the potential 
risks of participation. Patients will be clearly informed that their participation or responses will not 
affect their access to ongoing care at ZSFG cardiology clinics. ZSFG clinicians and Daniel's 
Pharmacy Staff who are recruited to participate in the exit interviews will be informed that their 
participation is optional. Any data collected will be stored in a de-identified manner and secured 

on a password protected server. Participants may choose to withdraw from the study at any 
point. Along with explicitly outlining of the study procedures, potential participants will be 
informed that they may choose to withdraw from the study at any point. Prior to consenting, 
participants will have an opportunity to ask any questions they may have. In addition to 
consenting to the pilot study, we will ask participants for consent to be contacted about related 
studies that they may be eligible for in the future. Patients who do not speak English will be 
excluded from the study. Only trained employees at UCSF will consent participants and manage 
protected health information (PHI) or personally identifiable data.
It is important that the people obtaining consent are qualified to do so.
*
Briefly describe the training and experience these individuals have in
obtaining informed consent: (REQUIRED)
All study team members have experience and certification for conduct of Human Subjects 
Research and have satisfied basic Collaborative Institutional Training Initiative (CITI) and Good 
Clinical Practice training requirements. Dr. Hsue’s research group has extensive experience 
conducting clinical research at ZSFG in both inpatient and outpatient settings. As the senior 
investigator on the study, Dr. Hsue will oversee the consent processes and ensure that informed 
consent is obtained in accordance to ZSFG and UCSF CHR standards.  
12.10  
Indicate how the study team will assess and enhance the subjects'
CONSENT COMPREHENSION: 
*
understanding of study procedures, risks, and benefits prior to signing the consent form (check all
that apply): (REQUIRED)   Tip: Review the Consent Comprehension - Learning Notes in the Help
bubble at the right for specific questions that can be asked to assess comprehension, consider
using the UCSF Decision-Making Capacity Assesment Tool, and review our guidance on obtaining
written or verbal informed consent for more detail on how to conduct the assessment.
The study team will engage the potential participant in a dialogue, using open-ended 
questions about the nature of the study or the experimental treatment, the risks and benefits 
of participating, and the voluntary nature of participation
Potential participants will be asked or shown a series of questions to assess their 
understanding of the study purpose, procedures, risks and benefits, as well as the voluntary 
nature of participation (especially appropriate when the consent process happens online or 
through a mobile health app)
Other method (describe below):
Provide details of the other approaches that will be used, if using another 
method to assess comprehension:
12.14  
What is the estimated time commitment for participants (per visit and in total):
TIME: 
PATIENTS:
The estimated on-site time commitment for participants, not including travel to and from ZSFG, 
will be approximately 5 hours:
Consent visit (30 minutes)
Intake visit (60 minutes)
5 study follow-up visits (30 minutes each): study week 0, 4, and 8 in--person and weeks 2 
and 6 by telephone
Exit interview (60 minutes)
In addition, participants will continue taking their heart failure medications (individually packaged 
vs. polypill) on a daily basis. 
CLINICIANS: 
The time commitment for clinician exit interviews will be approximately 1 hour. 
DANIEL'S PHARMACY STAFF:
The time commitment for pharmacy staff exit interviews will be approximately 1 hour. We will 
also conduct on-site observation of pharmacy staff at 2-3 visits in order to collect feasibility 
metrics about the time and cost of polypill production. During these site visits, the pharmacy staff 
will continue with their regular activities.

IMPORTANT TIP: Ensure this information is consistent with the 
information provided in the consent form.
12.15  
Is there a standard of care (SOC) or usual care that would be offered 
ALTERNATIVES: 
to prospective participants at UCSF (or the study site) if they did not participate in this research 
study:
 Yes  
 No
Describe the care that patients would ordinarily receive at the medical 
center if they did not participate in this study (provide details, assuming 
that some of the IRB members are not specialists in this field):
Patients who choose not to participate in the pilot trial will continue to receive standard care for 
their heart failure diagnosis, including all of the guideline-directed medications discussed above. 
The study intervention is co-packaging these medications into a single capsule for ease of use. If 
patients choose not to participate, they will continue to receive these medications, but they will 
be dispensed individually by the pharmacy. 
12.16  
Is the study drug or treatment available off-study:
OFF-STUDY TREATMENT: 
Yes 
No  
Not applicable 
13.0
Waiver of Consent/Authorization for Recruitment 
Purposes
This section is required when medical records may be reviewed to 
determine eligibility for recruitment.
13.1  
Study personnel need to access
* PRACTICABILITY OF OBTAINING CONSENT PRIOR TO ACCESS: 
protected health information (PHI) during the recruitment process and it is not practicable to obtain
informed consent until potential subjects have been identified: (REQUIRED)
Yes 
If 
, a waiver of consent/authorization is NOT needed.
no
13.2  
A waiver for screening of health records to identify potential subjects poses no
* RISK TO PRIVACY: 
more than minimal risk to privacy for participants:
Yes 
If 
, a waiver of authorization can NOT be granted.
no
13.3  
Screening health records prior to obtaining consent will not adversely affect
* RIGHTS/WELFARE: 
subjects' rights and welfare:
Yes 
If 
, a waiver of authorization can NOT be granted.
no
13.4  
Check all the identifiers that will be collected prior to obtaining informed consent:
* IDENTIFIERS: 

Names
Dates
Postal addresses
Phone numbers
Fax numbers
Email addresses
Social Security Numbers*
Medical record numbers
Health plan numbers
Account numbers
License or certificate numbers
Vehicle ID numbers
Device identifiers or serial numbers
Web URLs
IP address numbers
Biometric identifiers
Facial photos or other identifiable images
Any other unique identifier
None
Note: HIPAA rules require that you collect the minimum necessary.
13.5  
Describe any health information that will be collected prior to obtaining
* HEALTH INFORMATION: 
informed consent:
Since our study topic is a combination pill for patients wit HFrEF, with a specific interest in 
patients with concomitant HIV, our inclusion criteria specifies adults over 18 who carry an existing 
diagnosis of HFrEF (EF <40%) with or without a prior diagnosis of HIV.  We will rely on existing 
diagnoses, and we will not do any new testing to screen for study eligibility. To identify eligible 
participants, we will conduct targeted chart review on patients presenting to ZSFG cardiology 
clinics, the Positive Health Program and the ZSFG cardiology inpatient service. We will not collect 
any additional health information prior to obtaining informed consent, other than reviewing the 
chart for eligibility.
Note: HIPAA requires that you collect the minimum necessary.
13.6  
Describe your plan to destroy any identifiable data
* DATA RETENTION/DESTRUCTION PLAN: 
collected to determine eligibility for recruitment. This should be done at the earliest opportunity. If
you plan to retain identifiable recruitment data, provide the justification for doing so:
All data collected for study recruitment will be destroyed as soon as study recruitment has 
concluded.
14.0
Risks and Benefits
14.1  
Check if your study involves any of these specific research-related risks 
RESEARCH-RELATED RISKS: 
to participants that may need to be disclosed in the consent form:
For interventional studies, risk that the regimen may be more harmful or less effective than 
other available interventions
Risks associated with radiation exposure for imaging studies specifically for research purposes
Risks associated with the administration of contrast agent for imaging studies
Risks associated with withholding of treatment or discontinuation of current treatment (e.g., 
washout period is required by the study protocol)
For randomized, placebo-controlled trials, possible temporary or permanent health 
consequences from the deprivation of effective therapies during the placebo administration 

period
For studies involving a sham surgical procedure, the risk that participants may experience 
increased morbidity without the possibility of benefit
Risks associated with modification or extension of a surgical procedure primarily for research 
purposes (e.g. risks associated with prolonging anesthesia, time in the operating room, etc.)
Risk of pain or physical discomfort caused by the research intervention
Possible personal discomfort due to sensitive topics (stress, embarassment, trauma)
For any boxes checked above, describe how you will minimize these risks
*
and discomforts, e.g., adding or increasing the frequency
of monitoring, additional screening to identify and exclude people with
diminished kidney or liver function, or modification of procedures such as
changing imaging studies to avoid giving contrast agent to people who are
more likely to suffer side effects from it, etc.: (REQUIRED)
Since we are studying a packaging intervention of standard, FDA-approved therapies for heart 
failure, we anticipate that excess risk as a result of participation in our study will be low. 
However, heart failure therapies themselves carry risk including hypotension, hyperkalemia, and 
acute kidney injury. Participants may have increased exposure to these guideline-directed 
therapies due to either 1) new or higher-dose prescriptions from the study team, or 2) increased 
adherence to medications that are already prescribed. We will mitigate these risks by 1) excluding 
patients with contra-indications to heart failure guideline-directed medical therapies (GDMT), 
including advanced chronic kidney disease (eGFR <30), medication allergy, or pregnancy; and 2) 
maintaining an above-average follow-up schedule with at least monthly study visits. At these 
visits, patients will be screened for any adverse events, which will be reviewed by the research 
team. Any serious events will be reported to CHR and the study sponsor. 
14.2  
Describe any anticipated risks and discomforts not listed above: 
RISKS: 
*
(REQUIRED)
The following are possible risks of participation in this study. Overall we believe that this study 
meets the regulatory definition of minimal risk, i.e., "the probability and magnitude of harm or 
discomfort anticipated in the research are not greater than those ordinarily encountered in daily 
life or during the performance of routine physical or psychological examinations or tests." We 
base this determination on the fact that participants will be prescribed guideline-directed, FDA-
approved drugs at standard doses for heart failure. Current expert opinion supports starting 
several medication classes simultaneously or in rapid sequence for patients with heart failure (e.
g.
). All
https://jamanetwork.com/journals/jamacardiology/fullarticle/2777813
participants will be prescribed GDMT if not already prescribed and no contraindications exist. The
intervention is primarily a packaging intervention, akin to the use of a bubble pack or MediSet to
promote medication-taking adherence. The risk of side effects from these medications are not
significantly different than if the medications were prescribed simultaneously outside of a
research setting.
Potential risks to participants are described below:
Pilot trial:
Adverse effects of HFrEF medications: We hypothesize that over-encapsulation of HFrEF 
medications will lead to increased adherence to these medications among the intervention 
group. Patients may have increased exposure to these guideline-directed therapies due to 
either 1) intensification or uptitration of their regimen by the study team, or 2) increased 
adherence due to the polypill intervention. Increased utilization of these beneficial 
medications may also be associated with increased rates of documented adverse 
reactions. Adverse reactions to GDMT include hypotension, bradycardia, medication 
allergy, or hyperkalemia, which requires lab monitoring with any dose adjustment. To 
mitigate these risks, we will screen patients for contraindications at time of enrollment, 
and evaluate patients for adverse drug reactions at each follow-up visit. We will perform 
routine lab monitoring on participants, including evaluating for hyperkalemia. 
Possible dose adjustment of some heart failure medications: The standard dose of SGLT2 
for heart failure is one tablet of 10mg daily, however, some healthcare systems including 
the San Francisco VA prescribe a half-tablet of 25mg (i.e. 12.5mg daily). This difference is 
not thought to be clinically significant, and depends on the institution and formulary. In 
our prototyping, we found that only empagliflozin or dapagliflozin 12.5mg can be 
accommodated by the capsules. Thus, at time of study consent, we would ask participants 
for permission to adjust their SGLT2 dose from 10mg to 12.5mg daily if necessary. 
Similarly, some patients may be transitioned between clinically similar classes of beta 

blocker at comparable doses (i.e., from metoprolol succinate to bisoprolol due to pill size; 
or, from carvedilol twice-daily to carvedilol once-daily to be included in the polypill). From 
our clinical experience, these changes have minimal chance of harm, given that these 
changes will be between comparable agents at similar doses. However, there is a minimal 
risk that this slightly higher dose may increase side effects, which can include low blood 
pressure or low heart rate (beta blockers) or urinary frequency and dehydration (SGLT2 
inhibitor). To mitigate this risk, we will first confirm with the participant's primary 
cardiologist and/or primary care provider that this adjustment is likely to be safe. 
Participants will then be monitored with at least monthly visits and lab monitoring, which 
is more frequent than the typical standard of care. They will also be provided a study 
contact phone number in case of any medication-related adverse effects. The potential risk 
of empagliflozin side effects will be explained in detail to participants as part of the 
consent process.
Co-packaging and/or repackaging heart failure medications: As with bubble packs, 
changing packaging of prescription medications carries risk of medication error. We will 
partner with a pharmacy with experience in medication repackaging, and adhere to 
California State Board of Pharmacy regulations with regards to labeling and inclusion of 
prescription information. Daniel's Pharmacy frequently prepares bubble packs and 
MediSets for heart failure patients at ZSFG, which involves co-packaging individual tablets. 
As with these bubble packs, the polypills will be prepared by trained pharmacy technicians, 
and will undergo secondary review by a clinical pharmacist for accuracy before being 
delivered to the patient. 
Use of half-tablets: Some tablets may be cut in half by the pharmacist prior to inclusion in 
the poly-capsule. In compliance with U.S. Pharmacopeia General Chapter 795, half-tablets 
should be used within 6 months of pill cutting. This will be clearly labelled on the pill bottle 
and conveyed to study participants. 
Impact on adherence to excluded HFrEF medications: Any twice-daily HFrEF medications, 
such as sacubitril/valsartan, will have a second dose (e.g. the evening dose) which is 
omitted from the polypill and will continue to be dispensed individually. It is possible that 
this may change patients’ perceptions of cardiovascular medications that are not included 
in the polypill, or negatively impact adherence to those medications. At time of enrollment, 
we will discuss with patients that only some HFrEF tablets will be over-encapsulated, and 
reinforce the importance of all prescribed medications. We will monitor adherence to all 
HFrEF medications, antiretroviral therapy, and other prescriptions throughout the study 
period. Since total daily pill burden is a driver of non-adherence, we hypothesize that the 
polypill intervention will positively impact adherence to all prescriptions. 
Risk of medication error during crossover: At time of crossover, participants will switch 
from a polypill to individual tablets, or vice versa. This could carry a risk of taking double 
doses of some medications if they continue to take both dosage forms at once (e.g., 
continue to take some GDMT individually after starting the polypill). To mitigate this risk, 
we will ask participants to bring in all of their pill bottles to each study visit. When 
participants start the polypill, we will collect all individual GDMT pill bottles. When 
participants start the individual pill regimen, we will collect all remaining doses of the 
polypill. Individual pill bottles that are not expired can be returned to the participant at the 
end of the study period, if requested and if not expired. Identification and birth date will 
be confirmed prior to returning a participant's medications. 
Risk of missing multiple medications as a result of the polypill intervention: Our hypothesis 
is that the polypill will improve adherence; however, it may worsen adherence for some 
patients. When a patient misses a dose of a polypill, it would be equivalent to missing 
doses of several of their medications (rather than just one). To mitigate this risk, we will 
assess patients' adherence at each follow-up visit. We will ask patients to contact the 
study team sooner if they are having difficulty with the medication (e.g. not taking the 
polypill due to pill size), at which point we would determine the polypill to be intolerable 
for that patient, terminate the intervention, and resume all their medications as individual 
tablets. 
Risk of discomfort from pill size: The polypill will be larger than the individual component 
tablets, which could cause discomfort for some participants. We will show participants the 
projected polypill capsule size at time of study intake.
Specific risks related to observation of pharmacists: Direct observation of pharmacy 
technicians for the purposes of measuring feasibility metrics may cause some discomfort 
for those being directly observed, or may cause distraction which could impact their work. 
To mitigate this risk, we will ask participants' consent to be observed and will minimize 
interaction with participants while they are working. A pharmacist will review the work by 
pharmacy technicians as part of their standard safety procedures. Furthermore, there 
could be privacy concerns if the study team sees the names or medications of individuals 
who are not part of the study. We will discuss this risk with the pharmacists, and arrive at 
a strategy to minimize breach of confidentiality for patients who are not part of the study. 
Phlebotomy: Blood draws at follow-up visits could be associated with pain, bruising, or 
hematoma formation. Blood draws will be limited to under 10cc to minimize risk to 
participants from phlebotomy.

Breach of confidentiality: To minimize the risk of breach of confidentiality, all study staff 
will have completed CITI Human Subjects Protection Training and comply with privacy and 
data protection measures approved by the UCSF IRB. All appropriate measures will be 
taken for the protection of personally-identifiable health information (PHI), including de-
identification of all patient data objects.
Exit interviews: 
-Discomfort: For healthcare professionals (ZSFG clinicians or Daniel's Pharmacy staff), some
questions about their opinions on the study intervention may cause discomfort. For patients,
some questions about personal health practices or medication-taking adherence may make
patients feel uncomfortable. At the start of each interview, participants will be advised that they
may decline to answer any questions.
-Breach of confidentiality: as with other qualitative research, there is a risk of interviews being
overheard. As such, semi-structured interviews will be conducted in private rooms. Some
interviews may be conducted over telephone or secure video conferencing.
14.3  
MINIMIZING RISKS: Describe the steps you have taken to minimize the risks/discomforts to 
subjects. Examples include:
designing the study to make use of procedures involving less risk when appropriate
minimizing study procedures by taking advantage of clinical procedures conducted on the 
study participants
mitigating risks by planning special monitoring or conducting supportive interventions for the 
study
having a plan for evaluation and possible referral of subjects who report suicidal ideation
1. Informed Consent
Trained study investigators or clinical research coordinators will in-person informed consent 
discussions with each participant. The research staff will ensure that all questions have been 
addressed and the potential participant can confirm verbal understanding of the study’s purpose, 
intervention, basic procedures, and risk, as well as expresses confirmation that participation in 
the study is voluntary. If the patient chooses to participate, they will sign the consent form and 
will be given a signed copy to keep, along with the HIPAA form and UCSF Subject Bill of Rights.
Participants may stop the study at any time if they feel uncomfortable or do not wish to disclose 
any requested information. If participants decide to withdraw from the study, any information 
collected up to that point will be retained unless the participant requests the data be destroyed. 
We will not identify participants in reports to minimize risks associated with disclosure of their 
responses. Any alarming health care concerns expressed by the participants in the in-depth 
interviews will be referred to their individual healthcare provider after obtaining permission from 
the participant.
2. Standardized Protections Against Risk
Records for all subjects will be handled as confidentially as possible. Patient records will be coded 
and maintained in a locked office, and the research team will maintain copies of the signed 
consent forms. All digital records will be stored on password-protected, encrypted servers. 
Biologic specimens and clinical data will be linked to unique subject IDs, and not to any 
identifying patient information. 
3. Protection in the Event of Adverse Effects of Study Procedures
Patients will be monitored for adverse events throughout the study. The study will be conducted 
at ZSFG clinics, where there will be clinical staff available in case of any unanticipated severe 
adverse events. 
14.4  
Describe the resources in place to conduct this study in a way that assures protection 
RESOURCES: 
of the rights and welfare of participants:   These resources typically include appropriately trained 
and qualified personnel (in terms availability, number, expertise and experience), funding, space, 
  
equipment, and time to devote to study activities.  Depending on the nature of the research study, 
investigators should consider the proximity or availability of critical resources that may be essential 
to the safety and welfare of participants, such as
the proximity of an emergency facility for care of participant injury
availability of psychological support after participation
resources for participant communication, such as language translation services

Staff: 
The study team will include several attending cardiologists, including an advanced heart failure 
specialist. All of the study team will be appropriately trained and qualified for conduct of clinical 
research.
Location: 
Study follow-up visits will be conducted at ZSFG clinics, in close proximity to emergency response 
personnel in case of participant injury. Participants will be provided with a study contact phone 
number, as well as strict precautions to call 9-1-1 in case of a serious adverse event related to 
their medication.
Professional pharmacy services: 
Our pharmacy partner will be Daniel’s Pharmacy, which is certified community pharmacy with 
extensive experience with multi-dose packaging, including blister packs; MediSets; and over-
encapsulation.
Funding: 
This study will be funded by a UCSF CAPS-HIV Innovative Grant.
14.5  
BENEFITS: 
*
(REQUIRED) Note: These are the benefits that the IRB will consider during their review.
They are not necessarily appropriate to include in the consent form.
Possible immediate and/or direct benefits to participants and society at 
large (check all that apply):
Positive health outcome (e.g. improvement of condition, relief of pain, increased mobility, 
etc.)
Closer follow-up than standard care may lead to improved outcomes or patient engagement
Health and lifestyle changes may occur as a result of participation
Knowledge may be gained about their health and health conditions
Feeling of contribution to knowledge in the health or social sciences field
The research presents a reasonable opportunity to further the understanding, prevention, or 
alleviation of a serious problem affecting the health or welfare of children
Other benefit (describe below)
None
14.6  
Explain why the risks to subjects are reasonable in relation to anticipated 
RISK TO BENEFIT RATIO: 
benefits, if any, to the participant or society:
The primary benefit of this study is the knowledge of contributing to research, which could in the 
future lead to new delivery systems for heart failure medications. Secondly, participants will be 
seen more frequently than standard care, which could have potential health benefits. Finally, if 
the polypill is an effective adherence intervention, it may positively impact participants’ 
adherence to GDMT for the duration of the trial period. Participants will continue to pay standard 
medication copays if applicable, unless the copay is solely attributable to participation in the trial 
(for example, if they have a copay as a result of switching from metoprolol to bisoprolol for the 
purposes of the polypill intervention). 
We believe that the risks to participants are low, and will be further mitigated by close clinical 
follow-up for the duration of the pilot trial. Patients who choose to participate in the study will be 
contributing to research that we hope will improve access to cardiovascular therapies in the 
future. 
15.0
Data and Safety Monitoring Plan
15.1  
DATA AND SAFETY MONITORING PLAN (DSMP): 
*
(REQUIRED) Provide a summary of the DSMP:

All greater than minimal risk studies are required to provide a plan. 
Lack of an adequate plan is one of the most common reasons why 
IRB approval is delayed.
Instructions:
Describe the plan for monitoring data quality and participant safety. Key 
areas that should be included in the plan are:
An explanation of the plan to monitor data collection, study progress, 
and safety
A description of who will perform the monitoring and at what 
frequency (e.g., the PI only, a contract research organization, a Data 
and Safety Monitoring Board or Data Monitoring Committee, etc.)
The type of data and events that will be reviewed (e.g., adverse 
events, breaches of confidentiality, unanticipated problems involving 
risk to participants or others, unblinded efficacy data, etc.)
Procedures and timeline for communicating monitoring results to the 
UCSF IRB, the study sponsor, and other appropriate entities
As appropriate:
A plan for conducting and reporting interim analysis
Clearly defined stopping rules
Clearly defined rules for withdrawing participants from study 
interventions
Data and safety monitoring will be performed by the research team. At weekly research team 
meetings, any data events (including suspected breaches of confidentiality, unanticipated risks to 
participants or others, or other adverse events) will be reviewed by the study team. Any 
unforeseen data or safety events will be reported to the UCSF CHR within 7 days. 
Specifically, the study team will conduct internal interim safety analyses at 4 and 8 weeks. At 
these meetings, we will review safety data including preliminary impact on adherence (positive or 
negative); documented episodes of medication-related adverse effects; and any ER presentation 
or hospital admission of study participants. Any adverse events will be promptly reported to the 
UCSF CHR and the study sponsor (UCSF CAPS). If adverse events are possibly attributable to 
study procedures, potential outcomes could include: continue the study with increased monitoring 
schedule, stop the trial for a single participant or group of participants, or stop the study 
altogether. Precise stopping rules will be finalized after formative interviews with cardiologists and 
patients in qualitative Aim 1.
Additional information on the plan for confidential data collection and storage is outlined below.
Data Monitoring Plan to Ensure the Safety of Participants:
Recorded interviews will be stored as audio files on a password-protected, secure online server. 
Any alarming health care concerns expressed by the participants in the in-depth interviews will be 
referred to their individual healthcare provider after obtaining permission from the participant. 
Electronic surveys will be administered via REDCap and the link between identifiers and data will 
be destroyed after the completion of the study.
Data Banking:
Data will be retained for the duration of the study, and access will be limited to the research team 
outlined in this protocol. Data will be stored at UCSF within a secure, encrypted, password-
protected REDCap database server. Alter completion of the study, the link between identifiers and 
data will be destroyed.
Data Sharing:
 Any data shared with other institutions for ongoing research activities will be de-identified and 
password protected. De-identified data intended for research purposes may be shared upon 
written request to the Principal Investigators.
Provisions to Protect the Privacv and Confidentiality of Participants and the Research Data:
 Participants may choose to withdraw from the study at any point. Along with explicit outlining of 

the study procedures, this ability of participants to withdraw will be clearly stated to each 
participant at the start of each interview.
Audio Recording:
The key informant in-depth interviews will be audio recorded with the participant’s consent. Prior 
to the start of the recording, participants will be asked to provide a pseudonym or first name. 
Recording can be paused or stopped, if requested by participants, at any time.
Audio recordings will be copied to secure, encrypted, password-protected servers at UCSF. After 
audio transcription, all recordings on encrypted devices will be destroyed. De-identified 
transcripts and research records will be kept on secure, encrypted, password-protected servers at 
UCSF for a minimum of 7 years after the end of the study.
15.2  
DATA AND SAFETY MONITORING BOARD (DSMB): 
*
(REQUIRED) Will a Data and Safety Monitoring
Board (DSMB) be established:
Yes 
No 
Guidelines
A Data and Safety Monitoring Board (DSMB) or Data Monitoring Committee 
(DMC) is a formal, independent committee that is specifically established to 
conduct interim monitoring, oversight and analysis of study information and 
data to assure the continuing safety, efficacy, appropriateness, relevance, 
and integrity of the study.
The UCSF IRB reserves the right to request a DSMB/DMC for any study. 
However, the following are factors that the IRB will consider when making 
this determination:
There is a significant likelihood of a serious adverse event to subjects
The study is conducted at multiple sites and the level of risk is greater 
than minimal
The study generates data that are blinded or randomized
The study involves a large number of patients randomized to one of 
two or more interventions
A study for which the performance of an interim analysis is crucial for 
the protection of the subjects
First use in humans
First use in children
The study involves gene therapy, stem cell therapy, or other novel 
interventions for which long-term outcome data are not known or 
available
16.0
Confidentiality, Privacy, and Data Security
16.1  
Indicate how subject privacy will be protected: 
PROTECTING PRIVACY: 
*
(REQUIRED)
Conduct conversations about the research in a private room
Ask the subject how they wish to be communicated with – what phone numbers can be 
called, can messages be left, can they receive mail about the study at home, etc.
Take special measures to ensure that data collected about sensitive issues do not get added 
to their medical records or shared with others without the subject’s permission
Other methods (describe below)
16.2  
Do any of the instruments ask about illegal or stigmatized behavior: 
SENSITIVE DATA: 
*
(REQUIRED)

  Yes  
  No
16.3  
Could a breach of
SIGNIFICANT CONSEQUENCES OF A LOSS OF PRIVACY OR CONFIDENTIALITY: 
*
privacy or confidentiality result in any significant consequences to participants, such as criminal or
civil liability, loss of state or federal benefits, or be damaging to the participant's financial standing,
employability, or reputation: (REQUIRED)
  Yes  
  No
16.4  
Explain any extra steps that will be taken to assure 
EXTRA CONFIDENTIALITY MEASURES: 
confidentiality and protect identifiable information from improper use and disclosure, if any:
Study follow-up visits will be conducted on-site at ZSFG or by secure Zoom or telephone in 
private, quiet rooms. Interviews will be conducted by HIPAA-compliant Zoom, telephone, or in 
person in a quiet, private room in an affiliated ZSFG cardiology clinic. Recorded interviews will be 
stored as audio files on a password-protected, secure online server. Any alarming health care 
concerns expressed by the participants in the in-depth interviews will be referred to their 
individual healthcare provider after obtaining permission from the participant. Electronic surveys 
will be administered via REDCap and the link between identifiers and data will be destroyed after 
the completion of the study.
16.5  
Do you anticipate that this study may collect information that State or Federal
REPORTABILITY: 
*
law requires to be reported to other officials, such as elder abuse, child abuse, or threat to self or
others, or HIV status and other reportable conditions: (REQUIRED)
  Yes  
  No
16.6  
Will this study obtain a Certificate of Confidentiality:
CERTIFICATE OF CONFIDENTIALITY: 
*
(REQUIRED)
  Yes  
  No
16.7  
Will there be any sharing of 
 research test
SHARING OF RESEARCH RESULTS: 
*
EXPERIMENTAL
results with subjects or their care providers: (REQUIRED)
  Yes  
  No
16.9  
Study data will be: 
* HIPAA APPLICABILITY: 
(REQUIRED)
Derived from a medical record (e.g. APeX, OnCore, etc. Identify source below)
Added to the hospital or clinical medical record
Created or collected as part of health care
Used to make health care decisions
Obtained from the subject, including interviews, questionnaires
Obtained ONLY from a foreign country or countries
Obtained ONLY from records open to the public
Obtained from existing research records
None of the above
Derived from the Integrated Data Repository (IDR) or The Health Record Data Service 
(THREDS) at ZSFG
In addition to signing a consent form, each subject will have to sign 
the 
 
UCSF Participant Authorization for Release of PHI for Research
(HIPAA Form). Upload the HIPAA Form in the Other Study 

Documents section of the Initial Review Submission Packet Form. 
Failure to have patients sign the HIPAA Authorization is one of the 
most common findings from QIU Routine Site Visits.
Guidance about HIPAA requirements and other HIPAA-related forms
 are available online on the IRB's HIPAA page.
If derived from a medical record, identify source (UCSF Health APeX, 
SFDPH Epic, VA CPRS, etc.):
SFDPH Epic
16.10  
 Answer the following questions to determine if this study is subject to
* GDPR APPLICABILITY:
additional data privacy regulations under the General Data Protection Regulation (GDPR and/or UK
GDPR): (REQUIRED)
Is the study targeting or recruiting 
 or
*
European Economic Area (EEA)
United Kingdom (U.K.) participants, or collecting and using the personal
data of participants located in the EEA or the U.K.: (REQUIRED)
NOTE: If this study is being carried out online and may recruit 
people living in the EEA zone or the U.K., you should check 'Yes.'
  Yes  
  No
* Is the study receiving data from a site that is collecting data from
individuals located in the EEA or U.K. nations: (REQUIRED)
  Yes  
  No
16.11  
Will any of the following identifiers be collected and included in the research
IDENTIFIERS: 
*
records, even temporarily: (REQUIRED)
Names
Dates
Postal addresses (if only requesting/receiving zip codes check Yes to the Zip Code question 
below instead of checking this box)
Phone numbers
Fax numbers
Email addresses
Social Security Numbers*
Medical record numbers
Health plan numbers
Account numbers
License or certificate numbers
Vehicle ID numbers
Device identifiers or serial numbers
Web URLs
IP address numbers
Biometric identifiers
Facial photos or other identifiable images
Any other unique identifier
None
Could study records include 
 photos or images (even 'unidentifiable'
*
ANY
ones): (REQUIRED)

  Yes  
  No
16.13  
Will health information or other clinical data be accessed from UCSF
* PATIENT MEDICAL RECORDS: 
Health, Benioff Children's Hospital Oakland, or Zuckerberg San Francisco General (ZSFG):
(REQUIRED)
 Yes  
 No
16.16  
Does the research require access to any of
HIPAA - PERMISSION TO ACCESS SENSITIVE DATA: 
*
the following types of health information from the medical record: (check all that apply)
(REQUIRED)
Drug or alcohol abuse, diagnosis or treatment
HIV/AIDS testing information
Genetic testing information
Mental health diagnosis or treatment
None of the above
Important note: Ensure that participants initial the corresponding 
line(s) in Section C of the HIPAA authorization form during the 
consent process.
16.20  
(check all that apply): 
* DATA COLLECTION AND STORAGE: 
(REQUIRED)
Collection methods:
Electronic case report form systems (eCRFs), such as OnCore or sponsor-provided clinical trial 
management portal
UCSF ITS approved Web-based online survey tools: Qualtrics or RedCap
Other web-based online surveys or computer-assisted interview tool
Mobile applications (mobile or tablet-based)
Text Messaging
Wearable devices
Audio/video recordings
Photographs
Paper-based (surveys, logs, diaries, etc.)
Other:
What online survey or computer assisted interview tool will you use:
*
(REQUIRED)
Qualtrics (Recommended)
RedCAP (Recommended)
Survey Monkey (NOT recommended and may require UCSF ITS Security review)
Other
Data will be collected/stored in systems owned by (check all that apply):
*
(REQUIRED)
Study sponsor
UCSF data center (including OnCore, RedCap, Qualtrics, and MyResearch)
UCSF encrypted server, workstation, or laptop residing outside of UCSF data center
Personal devices, such as laptops or tablets that are not owned or managed by UCSF
San Francisco VA Health Care System (SFVAHCS)
Zuckerberg San Francisco General Hospital

Benioff Children's Hospital Oakland
Langley Porter Psychiatric Institution
Other UCSF affiliate clinic or location (specify below)
Cloud vendor such as Amazon Web Services (AWS), Salesforce, etc. (specify below)
Other academic institution
3rd party vendor (business entity)
Other (explain below)
16.21  
 Will patient records reviewed under this approval be
* ADDITION OF RECORDS TO A REGISTRY:
added to a research database, repository, or registry (either already existing or established under
this protocol): (REQUIRED)
  Yes  
  No
16.22  
During the lifecycle of data collection, transmission, and storage, will identifiable
DATA SHARING: 
*
information be shared with or be accessible to anyone outside of UCSF: (REQUIRED)
 Yes  
 No
* Who will have access to the data: (REQUIRED)
Collaborators listed in the study application
NIH or other shared data repository
Sponsors
FDA
Other 3rd party (such as vendors/contractors)
IMPORTANT: The IRB now recommends that all consent forms 
include a provision for sharing of de-identified/coded data to permit 
re-use of data for secondary research purposes. This doesn't apply 
if you've been granted a waiver of consent for this study.
Provide the details of whom the data will be shared with and what types
*
of information and identifiers will be shared: (REQUIRED)
Our pharmacist partner, Daniel's Pharmacy, will receive prescriptions for heart failure medications 
for study participants, which will include the patients' name, birth date and medical record 
number. The pharmacy will provide the medications as well as the packaging services, but will be 
in a contracting role and is not engaged in human subjects research. 
Our research collaborators at Washington University in St. Louis will assist with review of 
deidentified data for the purposes of analysis and manuscript preparation. This may include 
deidentified transcripts from exit interviews, which our Wash U collaborators may help to code 
and analyze. No identifiable patient information will be stored on Wash U servers, nor accessed 
by investigators outside of UCSF. 
16.23  
: How will data be securely shared with the 3rd party: 
* DATA SHARING METHODS
(REQUIRED)
Collaborators will access data in MyResearch
Collaborators will access data in REDCap
Collaborators will be sponsored as an affiliate and be treated as an UCSF user (includes using 
UCSF Box)
UCSF Secure Email will be used to share data
Collaborator’s or Sponsor’s system will be used (specify below)
Other method (describe below)
Please provide details about how the data will be shared:

Daniel's Pharmacy will receive electronic prescriptions for heart failure medications via SFDPH 
Epic, as is done in non-research settings. For study participants, the "Note to Pharmacy" will 
include instructions on co-packaging the pills into a heart failure polypill. The study team will also 
communicate frequently with Daniel's Pharmacy staff by telephone or secure email to track 
prescription fulfillment and delivery to study participants. 
17.0
Financial Considerations
17.1  
Will subjects be paid for participation or receive any other kind of compensation:
* PAYMENT: 
(REQUIRED)
 Yes  
 No
17.2  
Will participants be reimbursed for expenses related to study participation:
* REIMBURSEMENT: 
(REQUIRED)
 Yes  
 No
Describe the reimbursement that will be available to participants:
Bus tokens, parking vouchers, or other transportation vouchers will be provided as needed.
17.3  
Participant payment or compensation methods (check all
* PAYMENT/REIMBURSEMENT METHODS: 
that apply): (REQUIRED)
Payments will be (check all that apply):
Cash
Check
Gift card
Debit card
UCSF Research Subject Payment Card
Reimbursement for parking and other expenses
Other:
17.4  
Describe the schedule and amounts of payments, including the total subjects
* PAYMENT SCHEDULE: 
can receive for completing the study: (REQUIRED)
If there are multiple visits over time, explain how payments will be prorated for partial 
completion
If deviating from recommendations in Subject Payment Guidelines, include specific 
justification below
Participants will receive a $10 gift certificate for each visit, with an additional $30 if they bring in 
their pill bottles and an additional $10 for any blood draws that are needed for the purposes of 
the study. The gift card will be provided to participants at the time of each visit or interview. 
We will also offer $20 gift cards to patients and ZSFG clinicians for participation in a 30-60 minute 
exit interview. Daniel's Pharmacy staff will be paid for their time for exit interviews, as with their 
time spent manufacturing polypills, according to an hourly fee schedule.
The maximum compensation per participant will be approximately $260 ($10 each for up to 6 
trips to the hospital - including study and lab visits, $10 each for up to 6 lab draws, $30 each for 
bringing their pill bottles to the 4 study visits, and $20 for an exit interview).
17.5  
Will subjects or their insurance be charged for any study activities: 
 COSTS TO SUBJECTS: 
*

(REQUIRED)
 Yes  
 No
Describe the costs that may be incurred by subjects or 3rd party payers as 
a result of participation: 
Explain why it is appropriate to charge those costs to the subjects 
ompare subjects’ costs to the charges 
If this is a therapeutic study, c
that would typically be associated with receiving care off-study (e.g. is 
it more expensive to participate in this study than to receive care off-
study?)
There will be no cost to subjects, other than time provided to participate in the study. We will 
recruit participants on-site at ZSFG in order to avoid additional travel costs for patients; we will 
also provide bus tokens or travel vouchers if needed. 
Since the polypill is primarily a medication packaging intervention (like a bubble pack or 
MediSet), participants’ heart failure therapies will continue to be charged to their insurance, and 
they may be charged medication copays if applicable (although most patients enrolled in SF 
 
Health Plan or MediCal have zero copays for their heart failure medications). The total charges 
should be the same whether they are in the control arm (medications dispensed individually) or 
the polypill arm (medications packaged into a polypill at the pharmacy). 
Patients who are not already on guideline-directed heart failure therapies may be started on new 
medications at the start of the study, which could incur additional copays for the patient. Since 
study clinicians are all part of the ZSFG cardiology department, and since all the medications are 
standard guideline-directed therapies, we do not anticipate that there will be any differences in 
insurance coverage of medications that are prescribed during study visits vs. standard care visits. 
If there are additional costs that are specific to participation in the study (for example, needing to 
refill a patient's medications early because they enrolled in our polypill trial), those costs will be 
covered by the study team. Otherwise, standard copays will be paid by patients as usual.
As with a bubble pack, the polypill will require that some medications be picked up together on 
the same day (rather than filling individual medications on different days), which could result in a 
larger financial outlay at one time for patients with medication copays. As with a bubble pack or 
blister pack, dose adjustments for any component of the polypill will need to be implemented with 
the next month’s polypill packaging. For time-sensitive changes, the remaining supply of polypills 
will need to be repackaged or replaced by the pharmacy. Compared to standard care with a 
bubble pack, we do not anticipate that the trial will significantly impact pharmacy costs for 
patients or payors. 
18.0
Other Approvals and Registrations
18.1  
Does this study involve administration of vaccines
* ADMINISTRATION OF RECOMBINANT DNA: 
produced using recombinant DNA technologies to human subjects?  (REQUIRED)
  Yes  
  No
18.2  
Does this study involve 
 (also called "Human Gene 
* HUMAN GENE THERAPY: 
human gene therapy
Transfer": (REQUIRED)
  Yes  
  No
18.4  
Indicate if this study involves other regulated materials and requires approval 
OTHER APPROVALS: 
and/or authorization from the following regulatory committees:
Institutional Biological Safety Committee (IBC)

Specify BUA #:
Institutional Animal Care and Use Committee (IACUC)
Specify IACUC #:
Controlled Substances
19.0
Qualifications of Key Study Personnel and Affiliated 
Personnel
NEW: January 2019 - Affiliated personnel who do not 
need access to iRIS no longer need to get a UCSF ID. 
Instead, add them below in the Affiliated Personnel 
table below. 
19.1  Qualifications of Key Study Personnel:
Instructions:
For UCSF Key Study Personnel (KSP)* listed in 
 select the KSP 
Section 3.0,
from the drop down list and add a description of their study responsibilities, 
qualifications and training. In study responsibilities, identify every individual 
who will be involved in the consent process. Under qualifications, please 
include:
Academic Title
Institutional Affiliation (UCSF, ZSFG, SFVAHCS, etc.)
Department
Certifications
NOTE: This information is required and your application will be 
 
considered incomplete without it. If this study involves invasive or 
risky procedures, or procedures requiring special training or 
certification, please identify who will be conducting these 
procedures and provide details about their qualifications and 
training. Click the orange question mark for more information and 
examples. 
Training Requirements: 
The IRB requires that all Key Study Personnel complete Human Subjects 
Protection Training through 
 prior to approval of a new study, or a 
CITI
modification in which KSP are being added. More information on the CITI 
training requirement can be found on our 
. 
website  
* Definition of Key Study Personnel and CITI Training Requirements (Nov,
 UCSF Key Study Personnel include the Principal Investigator, other investigators
2015):
and research personnel who are directly involved in conducting research with study
participants or who are directly involved in using study participants’ identifiable private
information during the course of the research. Key Personnel also include faculty mentors
/advisors who provide direct oversight to Postdoctoral Fellows, Residents and Clinical
Fellows serving as PI on the IRB application.

KSP Name
Description of Study 
Responsibilities - Briefly 
describe what will each 
person be doing on the study. 
If there are procedures 
requiring special expertise or 
certification, identify who will 
be carrying these out. Also 
identify who will be obtaining 
informed consent.
Qualifications, Licensure, and 
Training
Dejong, Colette C
Principal investigator
Dr. Colette DeJong is a 
cardiology fellow and 
researcher at the 
University of California, 
San Francisco, with 
research experience in 
disparities in 
cardiovascular care.
Dr. Hsue, Priscilla MD, MD
Senior investigator, 
faculty mentor
Dr. Priscilla Hsue is the 
Maurice Eliaser Jr. 
Distinguished Professor 
of Medicine at the 
University of California, 
San Francisco, Chief of 
Cardiology at Zuckerberg 
San Francisco General 
Hospital, and Co-Director 
of the UCSF Center for 
Vascular Excellence. She 
is an international expert 
on the relation between 
inflammation, immune 
dysfunction, and 
cardiovascular disease. 
She has extensive 
experience conducting 
Phase II and Phase III 
clinical trials of anti-
inflammatory, 
immunomodulatory, and 
lipid lowering therapies 
for HIV, rheumatoid 
arthritis, atherosclerosis, 
and COVID-19.
Dr. Durstenfeld, Matthew 
S MD
Co-investigator
Dr. Matt Durstenfeld is a 
non-invasive general 
cardiologist and 
researcher with 
experience global 
cardiology, infectious-
disease related 
cardiovascular disease, 
and disparities in 
cardiovascular care. He is 
an Assistant Professor of 
Medicine at the 
University of California, 
San Francisco.
Co-investigator, 
Dr. Wayne Steward is a 
research psychologist 
with expertise in the 

Dr. Steward, Wayne PhD
qualitative methods 
expert
development of 
innovative care models 
for people with HIV.
Dr. Riley, Elise PhD
Co-investigator, 
epidemiologist
Dr. Elise Riley is an 
infectious disease 
epidemiologist and 
professor of medicine at 
UCSF, has extensive 
experience researching 
the combined effects of 
HIV, substance use, 
housing instability, and 
medical comorbidities on 
cardiovascular health.
Dr. Hickey, Matthew D MD
Co-investigator
Dr. Matt Hickey is a 
clinician and researcher 
based at Ward 86, with 
an interest in 
implementation science 
and novel approaches to 
expand access to care 
among PWH at ZSFG.
Dr. Zier, Lucas S MD
Co-investigator
Dr. Zier is an 
interventional 
cardiologist and 
researcher at ZSFG.
Schaffer, Veronica
Clinical research 
coordinator
Veronica Schaffer is a 
clinical research 
coordinator in Dr. 
Priscilla Hsue's group at 
ZSFG.
19.2  Affiliated Personnel:
Instructions:
This section is for personnel who are not listed in Section 3.0: Grant Key 
 because their names were not found in 
Personnel Access to the Study
the User Directory when 
 the iRIS Database and MyAccess directories 
both
were searched. Add any study personnel who fit 
 of the following criteria 
ALL
in the table below:
They meet the definition of Key Study Personnel (see above), and
They are associated with a UCSF-affiliated institution (e.g., SFVAHCS, 
Gladstone, Institute on Aging, Vitalant, NCIRE, SFDPH, or ZSFG), and
They do 
 have a UCSF ID, 
not
and
They do 
 need access to the study application and other study 
not
materials in iRIS.
 in the 
Note: Attach a CITI Certificate for all persons listed below
Other 
 section of the 
Study Documents
Initial Review Submission Packet 
 after completing the 
.
Form
Study Application

Click the orange question mark icon to the right for more information on 
who to include and who not to include in this section.
Do 
 list personnel from outside sites/non-UCSF-affiliated institutions. 
not
Contacts for those sites (i.e. other institution, community-based site, 
foreign country, or Sovereign Native American nation) should be listed in 
the 
 section of the application.
Outside Sites
If there are no personnel on your study that meet the above 
criteria, leave this section blank.
Name
Institution
Telephone
E-mail
Role
Christina Wang 
ZSFG 
628-206-0261
christina.s.
wang@sfdph.org
Other 
Investigator
Please describe the study responsibilities and qualifications of each affiliated 
person listed above:
Christina Wang, PharmD is an anticoagulation and cardiovascular pharmacist at ZSFG. She will be 
involved in the study as a co-investigator. As a DPH clinician, she will also be responsible for 
reviewing lists of potential participants that may be contacted for recruitment, in accordance with 
Research at SFDPH ZSFG Dean's Office protocol. 
20.0
End of Study Application
End of Study Application Form
: 
To continue working on the Study Application
Click on the section you need to edit in the left-hand menu. Remember to save through 
the entire Study Application after making changes.
:
If you are done working on the Study Application
Before proceeding, please go back to Section 4.0 Initial Screening 
Important: 
Questions and 
 through the form to make sure all the relevant 
Save and Continue
sections and questions have been included. If you've changed any answers since you 
started, the branching may have changed. Your application will be incomplete and it will 
have to be returned for corrections. 
Once you are sure the form is complete, click 
. If this is a new 
Save and Continue
study, you will automatically enter the 
, 
Initial Review Submission Packet Form
where you can attach 
or other 
. Review the 
consent forms 
study documents
Initial 
 for a list of required attachments.
Review Submission Checklist
Answer all questions and attach all required documents to speed up your 
approval.
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