Trial Outcomes & Findings for Heart Failure Polypill at a Safety Net Hospital (NCT NCT06029712)

NCT ID: NCT06029712

Last Updated: 2025-12-31

Results Overview

The primary outcome will be overall adherence to GDMT, as determined by pill count. We will first calculate the % adherence ratio for each prescribed class of GDMT (# pills missing / # pills supposed to be missing). The adherence ratio for each prescribed class of GDMT will then be averaged to derive the overall adherence ratio to GDMT. Pill count may be performed in-office or over videoconferencing.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 35 participants
• Primary outcome timeframe: The outcome will be measured 1) following a month of polypill use, and 2) following a month of individual tablet use.
• Results posted on: 2025-12-31

Participant Flow

Participant milestones

Measure	GDMT Delivered in a Heart Failure Polypill First (Individual Tablets Second) 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. This group is assigned to polypill first and individual tablets second.	GDMT Delivered as Individual Tablets First (Polypill Second) 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. After 1 month, participants assigned to individual tablets first will be switched to the polypill intervention.
Overall Study STARTED	17	18
Overall Study COMPLETED	14	13
Overall Study NOT COMPLETED	3	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Heart Failure Polypill at a Safety Net Hospital

Baseline characteristics by cohort

Measure	GDMT Delivered in a Heart Failure Polypill First (Individual Tablets Second) n=17 Participants 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. This group is assigned to polypill first and individual tablets second.	GDMT Delivered as Individual Tablets First (Polypill Second) n=18 Participants 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. After 1 month, participants assigned to individual tablets first will be switched to the polypill intervention.	Total n=35 Participants Total of all reporting groups
Age, Continuous	55 years n=1000 Participants	50.5 years n=1986 Participants	54 years n=2008 Participants
Sex: Female, Male Female	2 Participants n=1000 Participants	7 Participants n=1986 Participants	9 Participants n=2008 Participants
Sex: Female, Male Male	15 Participants n=1000 Participants	11 Participants n=1986 Participants	26 Participants n=2008 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=1000 Participants	0 Participants n=1986 Participants	1 Participants n=2008 Participants
Race (NIH/OMB) Asian	1 Participants n=1000 Participants	1 Participants n=1986 Participants	2 Participants n=2008 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=1000 Participants	1 Participants n=1986 Participants	2 Participants n=2008 Participants
Race (NIH/OMB) Black or African American	11 Participants n=1000 Participants	7 Participants n=1986 Participants	18 Participants n=2008 Participants
Race (NIH/OMB) White	3 Participants n=1000 Participants	7 Participants n=1986 Participants	10 Participants n=2008 Participants
Race (NIH/OMB) More than one race	0 Participants n=1000 Participants	0 Participants n=1986 Participants	0 Participants n=2008 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=1000 Participants	2 Participants n=1986 Participants	2 Participants n=2008 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=1000 Participants	4 Participants n=1986 Participants	6 Participants n=2008 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=1000 Participants	14 Participants n=1986 Participants	29 Participants n=2008 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=1000 Participants	0 Participants n=1986 Participants	0 Participants n=2008 Participants

PRIMARY outcome

Timeframe: The outcome will be measured 1) following a month of polypill use, and 2) following a month of individual tablet use.

Population: As part of the crossover analysis, the individual tablet periods were combined from both assignment groups (individual tablets first and polypill first), and the polypill periods were combined.

The primary outcome will be overall adherence to GDMT, as determined by pill count. We will first calculate the % adherence ratio for each prescribed class of GDMT (# pills missing / # pills supposed to be missing). The adherence ratio for each prescribed class of GDMT will then be averaged to derive the overall adherence ratio to GDMT. Pill count may be performed in-office or over videoconferencing.

Outcome measures

Measure	Individual Tablets n=27 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=27 Participants This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Measured Adherence to GDMT by Pill Count	74.6 adherence ratio expressed in % Interval 66.6 to 82.5	83.3 adherence ratio expressed in % Interval 75.3 to 91.3

SECONDARY outcome

Timeframe: The outcome will be measured 1) following a month of polypill use, and 2) following a month of individual tablet use.

Population: Included participants who had this measure for both study periods (polypill and individual tablets).

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.

Outcome measures

Measure	Individual Tablets n=26 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=26 Participants This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Morisky Medication Adherence-8 (MMAS-8) Questionnaire	4.1 Total Score Interval 3.4 to 4.8	4.6 Total Score Interval 3.9 to 5.4

SECONDARY outcome

Timeframe: The outcome will be measured 1) following a month of polypill use, and 2) following a month of individual tablet use.

Population: Included participants who had this measure for both study periods (polypill and individual tablets).

TSQM scores range from 0 to 100, with higher scores indicating greater treatment satisfaction.

Outcome measures

Measure	Individual Tablets n=26 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=26 Participants This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Treatment Satisfaction Using the Treatment Satisfaction Questionnaire for Medication (TSQM 9)	69.0 Points on Global Satisfaction Score Interval 61.6 to 76.3	73.6 Points on Global Satisfaction Score Interval 66.3 to 81.0

SECONDARY outcome

Timeframe: The outcome will be measured 1) following a month of polypill use, and 2) following a month of individual tablet use.

Population: For safety endpoints the number of participants included any participant who started that intervention period, so it is higher than then number analyzed who completed the efficacy outcome measures.

As a pilot trial, our study will not be powered for clinical outcomes, but key exploratory outcomes will include HFrEF admissions.

Outcome measures

Measure	Individual Tablets n=31 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=30 Participants This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Heart Failure Admission Rate	0 Participants	1 Participants

SECONDARY outcome

Timeframe: The outcome will be measured 1) following a month of polypill use, and 2) following a month of individual tablet use.

Population: Included participants who had this measure for both study periods (polypill and individual tablets).

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.

Outcome measures

Measure	Individual Tablets n=26 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=26 Participants This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Kansas City Cardiomyopathy Questionnaire (KCCQ) 12	67.9 Overall Summary Score Interval 59.6 to 76.3	70.6 Overall Summary Score Interval 62.2 to 78.9

SECONDARY outcome

Timeframe: The outcome will be measured 1) following a month of polypill use, and 2) following a month of individual tablet use.

Population: Included participants who had this measure for both study periods (polypill and individual tablets); for beta blockers this is 23, ACE/ARB/ARNI 23, MRA 26, and SGLT2i 22.

The investigators will calculate the adherence ratio for each individual component of GDMT (beta blocker, MRA, SGLT2i, and ACE/ARB/ARNI). This will be calculated as the (# pills missing) / (# pills supposed to be missing based on time elapsed between visits). This will allow us to investigate whether there is differential adherence to some categories of GDMT (for example, lower adherence to beta-blockers).

Outcome measures

Measure	Individual Tablets n=26 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=26 Participants This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Adherence Ratio to Individual Components of GDMT by Pill Count Beta Blockers	73.8 adherence ratio expressed in % Interval 64.7 to 82.8	83.6 adherence ratio expressed in % Interval 74.6 to 92.7
Adherence Ratio to Individual Components of GDMT by Pill Count ACE/ARB/ARNI	71.1 adherence ratio expressed in % Interval 61.0 to 81.1	80.4 adherence ratio expressed in % Interval 70.4 to 90.4
Adherence Ratio to Individual Components of GDMT by Pill Count MRA	74.4 adherence ratio expressed in % Interval 66.3 to 82.5	83.7 adherence ratio expressed in % Interval 75.6 to 91.8
Adherence Ratio to Individual Components of GDMT by Pill Count SGLT2i	73.4 adherence ratio expressed in % Interval 64.5 to 82.3	81.6 adherence ratio expressed in % Interval 72.7 to 90.4

SECONDARY outcome

Timeframe: The outcome will be measured 1) following a month of polypill use, and 2) following a month of individual tablet use.

Population: Included participants who had this measure for both study periods (polypill and individual tablets).

Systolic Blood pressure at baseline and study follow-up

Outcome measures

Measure	Individual Tablets n=26 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=26 Participants This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Blood Pressure (mmHg)	126 mm Hg Interval 118.0 to 134.0	124 mm Hg Interval 116.0 to 132.0

SECONDARY outcome

Timeframe: The outcome will be measured 1) following a month of polypill use, and 2) following a month of individual tablet use.

Population: Included participants who had this measure for both study periods (polypill and individual tablets).

Heart rate (beats per minute)

Outcome measures

Measure	Individual Tablets n=25 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=25 Participants This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Heart Rate	77 beats per minute Interval 71.0 to 84.0	77 beats per minute Interval 71.0 to 83.0

SECONDARY outcome

Timeframe: The outcome will be measured 1) following a month of polypill use, and 2) following a month of individual tablet use.

Population: Included participants who had this measure for both study periods (polypill and individual tablets).

Weight at baseline and study follow-up

Outcome measures

Measure	Individual Tablets n=20 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=20 Participants This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Weight	92.0 kg Interval 82.8 to 101.1	93.0 kg Interval 83.9 to 102.1

SECONDARY outcome

Timeframe: The outcome will be measured 1) following a month of polypill use, and 2) following a month of individual tablet use.

Population: Included participants who had this measure for both study periods (polypill and individual tablets).

Lab test

Outcome measures

Measure	Individual Tablets n=26 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=26 Participants This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
NT-ProBNP	1040.5 pg/ml Interval 448.4 to 1632.6	1086.5 pg/ml Interval 494.4 to 1678.7

SECONDARY outcome

Timeframe: 0, 2, 4, 6, and 8 weeks

Population: Safety endpoints include participants who started the intervention but did not complete it due to study dropout or loss to follow-up.

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.

Outcome measures

Measure	Individual Tablets n=31 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=30 Participants This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Adverse Events Any Adverse Event	6 Participants	7 Participants
Adverse Events Serious Adverse Events	1 Participants	1 Participants

SECONDARY outcome

Timeframe: The outcome will be measured 1) following a month of polypill use, and 2) following a month of individual tablet use.

Population: Included participants who had this measure for both study periods (polypill and individual tablets).

This will be calculated based on the patient's active medication list.

Outcome measures

Measure	Individual Tablets n=27 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=27 Participants This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Total Daily Pill Burden of the Patient	10 pills per day Interval 9.0 to 12.0	7 pills per day Interval 5.0 to 8.0

SECONDARY outcome

Timeframe: The outcome will be measured 1) at the start of the polypill intervention, and 2) at the start of the individual tablet intervention.

Population: This is measured at the start of each intervention period (because medication changes were only made for safety during each intervention period) so it includes all those who started each intervention period.

The number of GDMT pillars prescribed to the patient (BB, MRA, SGLT2i, and either ACEi, ARB, or ARNI) will be calculated at baseline and week 4.

Outcome measures

Measure	Individual Tablets n=31 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=30 Participants This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Number of GDMT Pillars Prescribed Beta Blocker	30 Participants	30 Participants
Number of GDMT Pillars Prescribed ACE/ARB/ARNI	28 Participants	28 Participants
Number of GDMT Pillars Prescribed MRA	30 Participants	29 Participants
Number of GDMT Pillars Prescribed SGLT2i	29 Participants	29 Participants

SECONDARY outcome

Timeframe: After study completion

Population: All participants who completed both intervention periods.

A Likert scale-style exit survey will be administered asking participants to compare their experience with the HFrEF polypill vs. individual tablets. 4 questions will comprise an Acceptability of Intervention Measure (AIM): 1) the polypill met my approval; 2) the polypill was appealing to me; 3) I liked the polypill; and 4) I welcomed the polypill as a treatment option for my heart failure. Each question includes a 5-point Likert scale, from 1 (strongly disagree) to 5 (strongly agree). Participants' responses to the 4 AIM questions will be averaged to comprise an AIM summary score.

Outcome measures

Measure	Individual Tablets n=27 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
HFrEF Polypill Patient Satisfaction Exit Survey	4.75 Score on a 5-point scale Interval 4.0 to 5.0	—

SECONDARY outcome

Timeframe: After study completion (between 8 and 12 weeks)

Population: All participants who completed both arms of the study.

Participation in a semi-structured exit interview using a RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, Maintenance)

Outcome measures

Measure	Individual Tablets n=27 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Number of Participants Completing a Qualitative Exit Interview	27 Participants	—

SECONDARY outcome

Timeframe: Assessed at week 0 or week 4

Population: The pharmacy measured the time it took them to prepare the polypills for a subset of participants.

Time required to prepare a 30-day supply of HFrEF polypill

Outcome measures

Measure	Individual Tablets n=9 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Implementation Outcome: Time Required to Manufacture the HFrEF Polypill at Our Community Pharmacy Partner	27 minutes Standard Deviation 4	—

SECONDARY outcome

Timeframe: Assessed at week 0 or week 4

Population: All participants who had polypills manufactured were included. The cost of manufacturing was the same for each patient, and was determined by the pharmacy partner (i.e. time and labor cost of preparing 1 month of polypill supply for 1 patient).

Cost of manufacturing a 30-day supply of HFrEF polypill

Outcome measures

Measure	Individual Tablets n=30 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Implementation Outcome: Cost of HFrEF Polypill Manufacturing at Our Community Pharmacy Partner	60 Dollars Standard Deviation 0	—

SECONDARY outcome

Timeframe: Assessed at weeks 4 and 8

Population: The analysis population includes all participants who started the intervention period and were not lost to follow up during that intervention period.

Number of days off GDMT due to a clinical event (e.g. hospitalization) or due to logistical / pharmacy issues

Outcome measures

Measure	Individual Tablets n=29 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=27 Participants This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Number of Days Off of GDMT 0 days	27 Participants	23 Participants
Number of Days Off of GDMT 1-3 days	1 Participants	3 Participants
Number of Days Off of GDMT 4-7 days	0 Participants	1 Participants
Number of Days Off of GDMT 8+days	1 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Completion of recruitment within 1 year of initiating recruitment

Population: This includes all participants who consented.

Number of months taken to recruit 30-40 people to consent to participate in the study

Outcome measures

Measure	Individual Tablets n=35 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Feasibility of Recruitment	6 months	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed following study completion (approximately 1 year)

Population: Number consented.

Successful completion of study related procedures for at least 20 participants (screening, randomization, drug allocation, follow-up procedures, retention, and transition to ongoing care)

Outcome measures

Measure	Individual Tablets n=35 Participants This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Feasibility of Adherence to Study Protocols	27 Participants	—

Adverse Events

Individual Tablets

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Polypill

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Individual Tablets n=31 participants at risk This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=30 participants at risk This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
Cardiac disorders Heart Failure Hospitalization	0.00% 0/31 • Adverse event data were collected from the time of starting the intervention period to the end of the intervention period.	3.3% 1/30 • Number of events 1 • Adverse event data were collected from the time of starting the intervention period to the end of the intervention period.
General disorders Non-Heart Failure Hospitalization	3.2% 1/31 • Number of events 1 • Adverse event data were collected from the time of starting the intervention period to the end of the intervention period.	0.00% 0/30 • Adverse event data were collected from the time of starting the intervention period to the end of the intervention period.

Other adverse events

Measure	Individual Tablets n=31 participants at risk This group represents the period of time during which participants were assigned to HF GDMT with individual tablets.	Polypill n=30 participants at risk This group represents the period of time during which participants were assigned to HF GDMT with a polypill.
General disorders Non-HF Emergency Department or Urgent Care Visit	3.2% 1/31 • Number of events 1 • Adverse event data were collected from the time of starting the intervention period to the end of the intervention period.	13.3% 4/30 • Number of events 4 • Adverse event data were collected from the time of starting the intervention period to the end of the intervention period.
Renal and urinary disorders Acute Kidney Injury	3.2% 1/31 • Number of events 1 • Adverse event data were collected from the time of starting the intervention period to the end of the intervention period.	6.7% 2/30 • Number of events 2 • Adverse event data were collected from the time of starting the intervention period to the end of the intervention period.
Renal and urinary disorders Hyperkalemia	3.2% 1/31 • Number of events 1 • Adverse event data were collected from the time of starting the intervention period to the end of the intervention period.	3.3% 1/30 • Number of events 1 • Adverse event data were collected from the time of starting the intervention period to the end of the intervention period.
General disorders Dizziness or Hypotension	6.5% 2/31 • Number of events 2 • Adverse event data were collected from the time of starting the intervention period to the end of the intervention period.	10.0% 3/30 • Number of events 3 • Adverse event data were collected from the time of starting the intervention period to the end of the intervention period.
General disorders GDMT Medication Discontinuation or Downtriation due Intolerance	3.2% 1/31 • Number of events 1 • Adverse event data were collected from the time of starting the intervention period to the end of the intervention period.	6.7% 2/30 • Number of events 2 • Adverse event data were collected from the time of starting the intervention period to the end of the intervention period.

Additional Information

Colette DeJong

Stanford University

Phone: 650-229-2482

Email: cdejong@stanford.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place