Clinical trial NCT06029712: Heart Failure Polypill at a Safety Net Hospital
Official title: Developing a Heart Failure Polypill to Improve Outcomes at a Safety Net Hospital: A Pilot Crossover Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure With Reduced Ejection Fraction
HIV Infections
Keywords: Medication adherence
Polypill
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2023-09-08
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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, the investigators will utilize inexpensive over-encapsulation techniques to develop a novel combination pill ("polypill") for patients with HFrEF. In Aim 1, the investigators will conduct stakeholder interviews with patients, providers, and pharmacists to inform the design of a HFrEF polypill. In Aim 2, the investigators will conduct a pilot, single-center, crossover randomized clinical trial to investigate whether, compared to usual care, a HFrEF polypill increases medication adherence among 20-40 adults with HFrEF. Given the high daily pill burden among patients with HIV and HFrEF, the investigators aim to recruit a subgroup of patients with HIV (\~10-20 participants) in addition to a subgroup of patients without HIV (\~10-20 participants).

Detailed description: 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)

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. The investigators 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. 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.

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 patient questionnaires will be collected, and additional GDMT agents may be prescribed by the study clinician if clinically indicated and there are no contraindications. At the first trial visit (week 0), baseline labs will be collected 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.

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).

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. 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.

Eligibility criteria: Inclusion criteria:

* Adults age 18+ with heart failure (current or prior NYHA stage II-IV)
* Ejection fraction \<50% on the most recent echocardiogram or MRI
* Last eGFR \> 30
* 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)
* Working phone number for telephone visits
* In addition to the inclusion criteria above, the investigators will preferentially recruit the following patient groups: people with HIV for a recruitment subgroup; patients who are less connected to cardiology care; people who are on \<4 pillars of GDMT, and have difficulty with medication adherence (as evidenced by detectable HIV viral load or refill gaps in Epic); and people who do not use bubble packs and do not have daily medication support staff for med administration.

Exclusion criteria:

* Patients who are not fluent in English (due to constraints of the small pilot trial)
* 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.

Primary outcomes:
measure: Measured adherence to GDMT by pill count
timeFrame: 4 and 8 weeks
Secondary outcomes:
measure: Morisky Medication Adherence-8 (MMAS-8) questionnaire
timeFrame: 0, 4, and 8 weeks
measure: Treatment satisfaction using the Treatment Satisfaction Questionnaire for Medication (TSQM 9)
timeFrame: 0, 4, and 8 weeks
measure: Heart failure admission rate
timeFrame: 0, 4, and 8 weeks
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ) 12
timeFrame: 0, 4, and 8 weeks
measure: Adherence ratio to individual components of GDMT by pill count
timeFrame: 0, 4, and 8 weeks
measure: Blood pressure (mmHg)
timeFrame: 0, 4, and 8 weeks
measure: Heart rate (beats per minute)
timeFrame: 0, 4, and 8 weeks
measure: Weight (lb)
timeFrame: 0, 4, and 8 weeks
measure: NT-ProBNP
timeFrame: 0, 4, and 8 weeks
measure: Adverse events
timeFrame: 0, 2, 4, 6, and 8 weeks
measure: Total daily pill burden of the patient
timeFrame: 0, 4, and 8 weeks
measure: Number of GDMT pillars prescribed at baseline, week 4, and week 8.
timeFrame: Baseline, week 4, and week 8
measure: HFrEF polypill patient satisfaction exit survey
timeFrame: After study completion (between 8 and 12 weeks)
measure: Exit interview (qualitative)
timeFrame: After study completion (between 8 and 12 weeks)
measure: Implementation outcome: time required to manufacture the HFrEF polypill at our community pharmacy partner
timeFrame: Assessed at week 0 or week 4
measure: Implementation outcome: Cost of HFrEF polypill manufacturing at our community pharmacy partner
timeFrame: Assessed at week 0 or week 4
measure: Number of days off of GDMT
timeFrame: Assessed at weeks 0, 4 and 8
measure: Medication discontinuation or down-titration due to intolerance
timeFrame: Assessed at weeks 0, 4 and 8
Other outcomes:
measure: Feasibility of recruitment
timeFrame: Completion of recruitment within 1 year of initiating recruitment
measure: Feasibility of adherence to study protocols
timeFrame: Assessed following study completion (approximately 1 year)
Locations:
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital
state: California
Study officials:
affiliation: University of California, San Francisco
name: Colette DeJong, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Priscilla Hsue, MD
role: PRINCIPAL_INVESTIGATOR
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