Heart Failure Polypill at a Safety Net Hospital
- Conditions
- HIV InfectionsHeart Failure With Reduced Ejection Fraction
- Interventions
- Drug: Heart failure polypillDrug: Control Rx
- Registration Number
- NCT06029712
- Lead Sponsor
- University of California, San Francisco
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description GDMT delivered in a heart failure polypill Heart failure polypill The polypill intervention will be pharmacy-level over-encapsulation of heart failure medications (beta-blocker, SGLT2 inhibitor, mineralocorticoid receptor antagonist, and ACE/ARB/ARNI) into a single capsule. For patients on twice-daily sacubitril/valsartan, one dose will be included in the polypill and the second dose will be dispensed separately. The investigators will partner with a local community pharmacy with proficiency in over-encapsulation. 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 vegan capsule. GDMT delivered as individual tablets Control Rx As described above, participants who are not already prescribed a beta blocker, SGLT2i, ACE/ARB/ARNI, and MRA will be initiated on these medications prior to randomization if no contraindications exist. Participants randomized to usual care will receive their heart failure medications as individual pills. They will have the option to receive medications by mail, clinic pick-up, or pharmacy pick-up.
- Primary Outcome Measures
Name Time Method Measured adherence to GDMT by pill count 4 and 8 weeks The primary outcome will be overall adherence to GDMT, as determined by pill count. Pill count may be performed in-office or over videoconferencing.
- Secondary Outcome Measures
Name Time Method Morisky Medication Adherence-8 (MMAS-8) questionnaire 0, 4, and 8 weeks The MMAS-8 scale consists of 8 items. Each of the first 7 items has 2 possible responses (yes/no), while the 8th item is answered with a 5-point Likert scale. The possible total medication adherence score ranges between 0 and 8, and the higher the score, the better the adherence level. A total score \< 6 is considered low adherence, while a total score of ≥ 6 but \< 8 indicates moderate adherence, and a score of 8 indicates high adherence.
Treatment satisfaction using the Treatment Satisfaction Questionnaire for Medication (TSQM 9) 0, 4, and 8 weeks TSQM scores range from 0 to 100, with higher scores indicating greater treatment satisfaction.
Weight (lb) 0, 4, and 8 weeks Weight at baseline and study follow-up
NT-ProBNP 0, 4, and 8 weeks Lab test
Heart failure admission rate 0, 4, and 8 weeks As a pilot trial, our study will not be powered for clinical outcomes, but key exploratory outcomes will include HFrEF admissions.
Kansas City Cardiomyopathy Questionnaire (KCCQ) 12 0, 4, and 8 weeks Exploratory clinical outcomes will include change in health-related quality of life as measured by the Kansas City Cardiomyopathy Questionnaire. KCCQ scores range from 0 to 100, with higher scores indicating higher quality of life.
Adherence ratio to individual components of GDMT by pill count 0, 4, and 8 weeks At study visits at 4 weeks and 8 weeks, the investigators will calculate the adherence ratio for each individual component of GDMT (beta blocker, MRA, SGLT2i, and ACE/ARB/ARNI). This will allow us to investigate whether there is differential adherence to some categories of GDMT (for example, lower adherence to beta-blockers).
Blood pressure (mmHg) 0, 4, and 8 weeks Blood pressure at baseline and study follow-up
Heart rate (beats per minute) 0, 4, and 8 weeks Heart rate at baseline and study follow-up
Adverse events 0, 2, 4, 6, and 8 weeks The investigators will document adverse events throughout the study period, for example, hyperkalemia, dizziness, or other medication-related side effects. The investigators will ask participants about adverse events at in-person visits (0, 4, and 8 weeks) and at telephone calls at approximately 2 and 6 weeks.
Total daily pill burden of the patient 0, 4, and 8 weeks This will be calculated based on the patient's active medication list.
Number of GDMT pillars prescribed at baseline, week 4, and week 8. Baseline, week 4, and week 8 The number of GDMT pillars prescribed to the patient (BB, MRA, SGLT2i, and either ACEi, ARB, or ARNI) will be calculated at baseline, week 4, and week 8.
HFrEF polypill patient satisfaction exit survey After study completion (between 8 and 12 weeks) A Likert scale-style exit survey will be administered asking participants to compare their experience with the HFrEF polypill vs. individual tablets.
Exit interview (qualitative) After study completion (between 8 and 12 weeks) In a semi-structured exit interview, participants will be asked about their experience with the HFrEF polypill vs. individual tablets.
Implementation outcome: time required to manufacture the HFrEF polypill at our community pharmacy partner Assessed at week 0 or week 4 Time required to prepare a 30-day supply of HFrEF polypill
Implementation outcome: Cost of HFrEF polypill manufacturing at our community pharmacy partner Assessed at week 0 or week 4 Cost of manufacturing a 30-day supply of HFrEF polypill
Number of days off of GDMT Assessed at weeks 0, 4 and 8 Number of days off GDMT due to a clinical event (e.g. hospitalization) or due to logistical / pharmacy issues
Medication discontinuation or down-titration due to intolerance Assessed at weeks 0, 4 and 8 Number of instances in which a HFrEF medication needs to be discontinued or down-titrated by the clinical study team
Trial Locations
- Locations (1)
Zuckerberg San Francisco General Hospital
🇺🇸San Francisco, California, United States