Wireless Automated Tracking in Cirrhosis Patients at Home (WATCH) Trial: A Randomized Single Blind Trial Testing the Use of Home Monitoring Among Decompensated Cirrhosis Patients
Phase: NA
Conditions: Cirrhosis, Liver, Portal Hypertension, Ascites Hepatic
Sponsor: University of California, San Francisco

Investigation of Ambulatory Blood Pressure in Cirrhosis Patients 
AmbBP-C Study
Hypothesis 
We will test the hypothesis that a proportion of patients with cirrhosis experience hypotension in the ambulatory 
setting, and this occurrence is associated with significant morbidity (e.g., acute kidney injury) and mortality. 
Aims: 
What is the burden of masked hypotension (i.e., Proportion of patients with normal clinic visit mean arterial 
blood pressure but with >1 episode of ambulatory hypotension)? 
What is the association between ambulatory blood pressure and clinic visit blood pressure and the 
development of acute kidney injury? 
What is the association between ambulatory blood pressure and clinic visit blood pressure and death? 
Design: 
This is an observational study. We will approach patients with cirrhosis who are seen at the outpatient UCSF 
Liver Clinics. If willing, patients will be provided an ambulatory blood pressure monitor with an integrated 
cellular signal (i.e., not wifi or bluetooth) that is listed on the US Blood Pressure Validated Device database 
(VDL). After an instructional meeting at the time of enrollment, participants will be asked to take their 
ambulatory blood pressure twice daily (i.e., morning and night). Participants will partake in this study for 1-year. 
The ambulatory data will be provided to the researchers through an encrypted, HIPAA compliant server 
provided by the blood pressure monitor manufacturer (i.e. Withings). Simultaneously, we will periodically (i.e., 
monthly) review the participant's medical records and will extract clinic visit notes including clinic visit blood 
pressure measurements, demographics, hospitalization records, and all available laboratory values. After 1-
year, the cellular signal on the device will be disabled. The participant will be able to keep the device for their 
own personal use. After 1-year, we will review their records every 6 months for an additional 2-years (3-years 
total). We will investigate the proportion of patients who experience masked hypotension. We will determine 
the association between ambulatory blood pressure and clinic visit blood pressure and the development of AKI 
and mortality. 
Background and Significance: 
Cirrhosis affects 1 in every 50 US adults and is the 4th leading cause of death in those ages 45-64 years.   
Acute kidney injury (AKI) in patients with cirrhosis is: i) common, occurring in one of every two patients; ii) 
lethal with nearly 75% of patients having AKI at death; iii) expensive, hospitalizations in cirrhosis patients with 
AKI cost ~$2 billion in 2016. A common risk factor of AKI in cirrhosis patients is hypotension. Patients with 
cirrhosis intrinsically have low blood pressure - a consequence of the altered venous return from portal 
hypertension and the impaired degradation by the liver of endogenous vasodilatory molecules. Despite this 
association, blood pressure in cirrhosis patients is currently only measured sparsely - every 3 to 6 months at 
Document Date: October 1, 2023
NCT05928624  

clinic visits. As a result, the burden of ambulatory hypotension and the impact of ambulatory hypotension on 
AKI and mortality in this population are unknown. 
 
Preliminary Studies: 
To date, no study in cirrhosis patients has investigated ambulatory blood pressures in cirrhosis patients. One 
study by Tsien et al has investigated the association between clinic visit blood pressure and the development 
of AKI. No study has investigated the association between ambulatory or clinic visit blood pressure on mortality 
in cirrhosis patients. 
 
Procedures/Methods: 
Patients will undergo the following procedures to this study: 
  
1. We will pre-screen patients coming to the UCSF outpatient liver clinic 48 hours prior to their visit. 
2. To set the device and allow for distribution at the time of their visit, we will call all possible participants 48 
hours prior to their clinic visit and determine if they are interested in partaking in this study.  
3. After their clinic visit, potential participants will be approached and provided the consent for this study. If 
willing, participants will be enrolled, provided a 5-minute device tutorial, and participants will be given the 
device on their visit day.  
4. After which, participants will complete a morning blood pressure (e.g., prior to breakfast) and nighttime blood 
pressure (e.g., prior to sleep) for 1-year.  
5. Patients at the time of enrollment will elect if they would like free text message reminders if they do not 
complete their measurements for a 24-hour period. If participants, do not complete their measurements for a 
72-hour period, then a member of the research team will call them to remind all patients.  
6. Should patients be hospitalized or traveling, we will instruct patients to not perform any measurements.  
7. All measurements will be provided to the researchers through an encrypted, HIPAA compliant portal 
provided by the manufacturer (Withings).  
8. We will review their medical records monthly for a 1-year period and every 6 months for an additional 2-year 
period. This review will include all clinic notes, demographics, and laboratory values. 
  
There will be no extra clinic visits, lab tests, biopsies, tissue collection, or additional scans outside the routine 
care and monitoring provided by the UCSF Liver Clinic. We will not monitor the portal for episodes of 
hypotension in real-time - meaning that if a patient has hypotension, they will not be called to review for 
symptoms. Instead, at the time of consent and the monitor tutorial, we will review with patients the signs and 
symptoms of hypotension. We will instruct patients to review any new developments with their provider, who 
can be reached 24 hours 7-days a week through the clinic number, or to seek urgent/emergent care. 
 
Statistical Methods 
We will divide our cohort into 4 groups: Ambulatory Hypotension/Clinic Hypotension, Ambulatory Normotension/Clinic 
Normotension, Ambulatory Hypotension/Clinic Normotension, Ambulatory Normotension/Clinic Hypotension.  
  
Our primary outcome will be acute kidney injury, defined as a doubling in serum creatinine from outpatient baseline requiring 
hospitalization. Baseline will be defined as the most recent outpatient serum creatinine prior to enrollment in this 
study.  Death will be defined as death.  
  
Survival analyses will determine the unadjusted and adjusted association of our 4 groups and AKI and death. We will censor 
those lost to follow-up. We will adjust for the variables obtained during our record review.  
 
References 
Cullaro, Giuseppe, Meyeon Park, and Jennifer C. Lai. 2018. “‘Normal’ Creatinine Levels Predict Persistent Kidney Injury and 
Waitlist Mortality in Outpatients With Cirrhosis.” Hepatology  68 (5): 1953–60. 
Cullaro, Giuseppe, Elizabeth C. Verna, and Jennifer C. Lai. 2019. “Association Between Renal Function Pattern and Mortality 
in Patients with Cirrhosis.” Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the 
American Gastroenterological Association 17 (11): 2364–70. 

Cullaro, Giuseppe, Elizabeth C. Verna, Brian P. Lee, and Jennifer C. Lai. 2020. “Chronic Kidney Disease in Liver Transplant 
Candidates: A Rising Burden Impacting Post–Liver Transplant Outcomes.” Liver Transplantation: Official Publication 
of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 26 
(4): 498–506. 
Tsien, Cynthia D., Rania Rabie, and Florence Wong. 2013. “Acute Kidney Injury in Decompensated Cirrhosis.” Gut 62 (1): 
131. 
Moon, Andrew M., Amit G. Singal, and Elliot B. Tapper. 2019. “Contemporary Epidemiology of Chronic Liver Disease and 
Cirrhosis.” Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American 
Gastroenterological Association 18 (12): 2650–66. 
Baki, Jad A., and Elliot B. Tapper. 2019. “Contemporary Epidemiology of Cirrhosis.” Current Treatment Options in 
Gastroenterology 17 (2): 244–53. 
Sample Size Justification 
Based on prior literature, we suspect the following distribution in our 4 groups: 50% ambulatory 
normotensive/clinic normotensive; 25% ambulatory hypotensive/clinic hypoptensive; 12.5% ambulatory 
hypotensive/clinic normotensive; 12.5% ambulatory normotensive/clinic hypotensive. As best we can estimate 
20% of the ambulatory normotensive/clinic normotensive group; 45% of the ambulatory hypotensive/clinic 
hypoptensive group; 40% of the ambulatory hypotensive/clinic normotensive; and 40% of the ambulatory 
normotensive/clinic hypotensive group will develop AKI during 1-year of follow-up. Based on these effect sizes, 
we found that we would need to recruit 274 patients to have 80% power to detect at a significance level of 
0.05. 
 
Age Range: 
18-64 
65+ 
 
Study Populations: 
Outpatients 
 
Special Subject Groups: 
Subjects unable to read, speak or understand English 
 
Roughly <10% of our population at the UCSF Liver Clinic are non-English speaking. The majority of these patients are either 
Cantonese, Mandarin, or English speaking. Through our clinic infrastructure, we have access to either in-person or video 
interpreters (Language Lines Solutions). Not including these potential participants would create a bias in our study based on 
English-speaking status. Given that we have available interpreter services and the minimal risk associated with this study, 
we feel that we can accurately and safely include these participants in our study.  
 
We will evaluate the capacity of the individual to consent for this study by confirming with their outpatient provider that they 
have capacity.  
  
We will provide the consent information in the participant's native language. We will ask them to perform teach-back to 
confirm comprehension.  
  
We have designed the payment for this study to reflect the amount of time needed to participate. 
 
Inclusion criteria: 

We will approach all patients with cirrhosis who are seen at the outpatient UCSF Liver Clinic. 
 
Recruitment and Consent 
 
We will pre-screen the UCSF Liver Clinic schedule and identify patients with a diagnosis of cirrhosis. This will include a review 
of patients' conditions, history, test results, etc.  
 
Searching of Medical Records 
Investigators' own patients or patients seen within the same practice 
Self-search in APeX or other medical records source 
We have an ongoing relationship with the Department of Medicine bioinformatics group. We in the future will develop a 
cohort selection tool that automates the selection of patients who are eligible for this study.  
 
Determination of Eligibility: 
Eligibility will be determined by the study team after the chart review as outlined above. This will include a patient seen in 
the UCSF liver clinic with a chart diagnosis of cirrhosis, medications for a cirrhosis indication, a cirrhosis-related complication, 
or laboratory values (thrombocytopenia, elevated total bilirubin, elevated INR, low albumin level) suggestive of cirrhosis.  
 
Initiation of Contact 
Investigators/study team 
 
How is contact initiated: 
In person, phone 
 
Recruitment Plan 
A member of our research team will review all UCSF outpatient liver clinics in the following 48 hours to screen 
which patients are presenting with a cirrhosis diagnosis.  
  
Each potential participant will be called 48 hours before their visit to see if they would be willing to meet with 
the research team after their clinic visit.  
  
Those who are willing will be met after their clinic visit by our research team either in-person or virtually via 
zoom that will be set up by our clinic staff. We will then discuss the consent process as outlined below. 
 
Consent Methods: 
Sign a paper consent form at the end of the consent discussion (signed consent) 
Sign an electronic consent form using DocuSign (signed consent) 
 
Consent Procedures: 
The outpatients are scheduled to be seen by a provider in the UCSF liver clinic. After their visit, they will meet 
either in-person or virtually via zoom with a member of our research team. If this meeting is virtual, our clinic 
staff will facilitate the meeting via an available clinic room in the same office building. Consent will be obtained 
by a member of the investigation team. This will be a ~ 15-minute meeting where the consent will be reviewed. 

After this meeting, the potential participant will be asked about consent. If they are willing, we will proceed. if 
they would like further information, we will approach patients at their subsequent clinic visit. If consent is 
obtained, we will provide an additional 5-10 minute tutorial on how to use the blood pressure monitor. We will 
review signs and symptoms of hypotension and ensure that all participants express understanding regarding 
the study, the indications to seek urgent/emergent care, and the clinic's 24-hour number. 
 
The study team has undergone training to consent patients for clinical studies. The principal investigator will review this 
consent with each member of the study team.  
 
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 
 
Given that <10% of our patients with cirrhosis in the UCSF Liver Clinic are non-English speaking, we do not foresee that we 
will need to consent non-English speaking patients often. Additionally, given the minimal risks associated with this study, we 
believe that it is reasonable to utilize the Short-Form.  
 
This study involves 2, 1-minute blood pressure measurements daily for 1 year. That is roughly 12-hours of time 
for year. Patients will be compensated for this time in 2 ways: 1). All patients will be able to keep their 
ambulatory blood pressure monitor after the study ($85 value); 2). Participants who complete >75% of their 
daily blood pressure measurements will receive a $25 Target gift card every 3 months for 1 year. 
 
Risks and benefits: 
 
Risk of pain or physical discomfort caused by the research intervention 
 
There is the risk of discomfort with the measuring of ambulatory blood pressure.  
  
There is the risk of loss of protected health information.  
  
There is the risk of undiagnosed hypotension.  
 
We have minimized the risk of pain by: 1) We will during our tutorial perform a monitored blood pressure 
measurement in the clinic. We will ensure that it is tolerated by the patient and if there are any concerns, the 
participant can withdraw from the study; 2) We have limited our measurements to just twice daily. This should 
limit the inconvenience to the participant.  
  
We will take several steps to protect PHI. All records and patient identifiers will only be kept in an encrypted 
REDCAP database. When exporting data or completing analyses, we will only use identifiers uniquely 
generated for this study. We have partnered with Withings who provides a HIPAA compliant, encrypted server 
to provide the ambulatory blood pressure measurements to the research team.  
  
There is the risk that patients will experience hypotension in the outpatient setting. That being said, typically 
this information is not available to providers. Therefore, this is not an added risk to what is tolerated normally. 
To mitigate this risk, during our tutorial we will review the signs of hypotension and indications to seek 

urgent/emergent care. Additionally, we will provide the clinic number with 24-hour, 7-days a week coverage 
should there be uncertainty or clinical questions. This service is available to all members of our practice. 
 
Resources 
Our staff is all clinically trained in clinical research including in the consent of patients and safe and responsible 
conduct in clinical research.  
  
We have obtained cellular-enabled devices that do not require WIFI or Bluetooth connection. As a result, this 
obviates many financial inequities that may present with the utilization of most ambulatory blood pressure 
monitors in clinical research.  
  
our clinic has the staffing and resources to provide the time and space to consent patients and inform patients 
about this study.  
  
We have access to our clinic answering service and we will provide the clinic number with 24-hour, 7-days a 
week coverage should there be uncertainty or clinical questions regarding possible hypotension symptoms. 
 
Benefits 
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 
 
Risk to benefit Ratio: 
The measurement of ambulatory blood pressure is a minimally invasive procedure. We have taken several 
steps to limit the risks to the participant. There is a marked opportunity to improve the care for the participant. If 
they are having hypotension, they can review these values with their provider. they may recognize behaviors 
that lead to hypotension and change those. There is significant potential to understand better how blood 
pressure mediates outcomes in cirrhosis patients. This may allow for future studies and clinical trials where 
blood pressure is modulated with vasoconstricting medications. 
 
Confidentiality 
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 

No stigmatized or illegal behavior will be obtained 
No breach of confidentiality could lead to significant consequences to the participant 
We will only leave PHI in the REDCAP database. We will utilize a study-specific, uniquely generated patient identifier for any 
analysis or export of the data outside of the REDCAP database.  
 
HIPAA Applicability: Study Data will be Derived from a medical record (e.g. APeX, OnCore, etc. Identify source below) 
 
Clinical Data: 
Study investigators or their designees will be responsible for data collection from the patient's medical chart using 
standardized methodologies described below. We propose to perform a manual chart review on a subsample of outpatients 
from the UCSF liver clinic. No sensitive information.