Heart Failure
Conditions
Brief summary
This study will investigate the effectiveness of two contextual just-in-time adaptive interventions (JITAIs) delivered via a mobile app for heart failure patients.
Detailed description
The Manage HF study is a multicenter 12-week randomized controlled double-blind 2x2 factorial clinical trial. This study will investigate the effectiveness of two contextual just-in-time adaptive interventions (JITAIs) delivered via a mobile app for heart failure patients. The clinical worsening intervention targets self-management of behaviors to prevent worsening of a patient's heart failure symptoms. The dietary sodium intervention promotes lower sodium intake. Eligible participants will be randomized to the dietary sodium intervention, the clinical worsening intervention, both interventions, or no intervention in a 1:1:1:1 manner, stratified by site, gender, and HF type (HFpEF versus HFrEF).
Interventions
BEHAVIORALSodium intervention
The sodium dietary intervention provides the user with a tailored message to assist with making dietary choices based on sodium content when they arrive at a grocery store or restaurant.
BEHAVIORALClinical worsening intervention
The intervention adapts to the participant's reported symptoms and provides feedback with a global health status indicator (HSI). Users will receive tailored push notification based on their HSI status.
BEHAVIORALEducational content
Standard heart failure educational information and a daily symptom survey.
Sponsors
University of Michigan
National Institute on Aging (NIA)
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years and older at screening 2. Currently admitted or discharged from the hospital within the last 14 days with a diagnosis of acute or acute on chronic decompensated HF. 3. Based on one of the EF criteria (LVEF within 12 months of randomization. BNP or NT-proBNP criteria within 30 days prior to randomization): * Left ventricular ejection fraction (LVEF) ≤ 40%. * LVEF \>40% and BNP \> 175 pg/ml or NT-proBNP \> 700 pg/ml. Thresholds for NT-proBNP and BNP for LVEF \> 40% will be corrected for body mass index (BMI) using a 4% reduction per BMI unit over 25 kg/m2. 4. Have a personal physician for follow-up 5. A smartphone with a compatible Apple or Android operating system installed and able to download and use ManageHF including accepting all permissions 6. A valid email address 7. Fluent in spoken and written English
Exclusion criteria
1. Contraindication to recommending a sodium restriction diet 2. Scheduled intervention for primary valvular heart disease will occur during the study period. 3. Cardiac resynchronization therapy (CRT) within 3 months prior to screening or current plan to implant CRT device during the study period. 4. Dialysis 5. Previous cardiac transplantation or implantation of a ventricular assistance device or similar device. 6. Listed status 1, 2 or 3 for heart transplant 7. Implantation of a ventricular assistance device is expected within 3 months after randomization 8. Non-cardiac illness with expected survival of less than 3 months 9. Discharge to a setting other than home 10. Requirement for chronic inotropic therapy (e.g. milrinone, dobutamine) 11. Inability to use Withings devices due to equipment limitations or contraindications 12. Currently pregnant or intend to become pregnant during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hierarchical Combination ("Win Ratio") of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | 12 weeks | Time to all-cause mortality (ACM), time to heart failure hospital readmission (HFHR), and decline in quality of life will be analyzed using the Finkelstein-Schoenfeld method. The method combines these three endpoints in a hierarchical fashion using ACM first, HRHR second, and change in HRQOL third. The method pairs every participant receiving the diet intervention with every participant not receiving the diet intervention within each stratum. Within each pairing, a +1 is assigned to the "better" participant, -1 to the "worse" participant, and 0 if they are "tied". The comparison begins with ACM. Tied pairings are then compared using HFHR. Any remaining tied pairings are compared using change in HRQOL. A 'Win' represents a participant doing better within each pairing (receiving +1) based on the hierarchical comparison. The reported unit is the total "wins" for each intervention group from performing such a hierarchical comparison across all strata. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-Cause Mortality [ Time Frame: Baseline up to Week 12 ] | 12 weeks | Time to all-cause mortality will be analyzed up to week 12. |
| Heart Failure-related Hospitalizations [ Time Frame: Baseline up to Week 12 ] | 12 weeks | Time to first heart-failure related hospitalization will be analyzed up to week 12. |
| Change From Baseline in Health-related Quality of Life [ Time Frame: Baseline up to Week 12 ] | 12 weeks | Change from baseline to week 12 in health-related quality of life as measured by the Minnesota Living with Heart Failure Questionnaire. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichael Dorsch, PharmD
University of Michigan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Group Standard heart failure educational information.
Educational content: Standard heart failure educational information and a daily symptom survey. | 12 |
| Dietary Sodium Intervention The dietary sodium intervention facilitates lower sodium choices using tailored push notifications.
Sodium intervention: The sodium dietary intervention provides uses location services to determine when a participant is at home, arrives at a grocery store or arrives at a restaurant. The user receives a tailored message to assist with making dietary choices based on sodium content. | 20 |
| Clinical Worsening Intervention The clinical worsening intervention promotes self-monitoring and self-management and is linked tailored push notifications.
Clinical worsening intervention: The intervention adapts to the participant's reported symptoms and provides feedback with a global health status indicator (HSI). Users will receive tailored push notification based on their HSI status. | 12 |
| Dietary Sodium and Clinical Worsening Full access to all content in the control, dietary sodium, and clinical worsening interventions.
Sodium intervention: The sodium dietary intervention provides uses location services to determine when a participant is at home, arrives at a grocery store or arrives at a restaurant. The user receives a tailored message to assist with making dietary choices based on sodium content.
Clinical worsening intervention: The intervention adapts to the participant's reported symptoms and provides feedback with a global health status indicator (HSI). Users will receive tailored push notification based on their HSI status. | 18 |
| Total | 62 |
Baseline characteristics
| Characteristic | Control Group | Dietary Sodium Intervention | Clinical Worsening Intervention | Dietary Sodium and Clinical Worsening | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 4 Participants | 2 Participants | 6 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 16 Participants | 10 Participants | 12 Participants | 46 Participants |
| Age, Continuous | 56.8 years STANDARD_DEVIATION 13.04 | 54.1 years STANDARD_DEVIATION 15.6 | 54 years STANDARD_DEVIATION 11.53 | 54.8 years STANDARD_DEVIATION 16.6 | 54.8 years STANDARD_DEVIATION 14.44 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 19 Participants | 12 Participants | 18 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 13 Participants | 7 Participants | 7 Participants | 34 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 6 Participants | 5 Participants | 10 Participants | 25 Participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 4 Participants | 6 Participants | 20 Participants |
| Sex: Female, Male Male | 9 Participants | 13 Participants | 8 Participants | 12 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 20 | 0 / 12 | 0 / 18 |
| other Total, other adverse events | 3 / 12 | 4 / 20 | 3 / 12 | 2 / 18 |
| serious Total, serious adverse events | 5 / 12 | 9 / 20 | 4 / 12 | 6 / 18 |
Outcome results
Primary
Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ]
Time to all-cause mortality (ACM), time to heart failure hospital readmission (HFHR), and decline in quality of life will be analyzed using the Finkelstein-Schoenfeld method. The method combines these three endpoints in a hierarchical fashion using ACM first, HRHR second, and change in HRQOL third. The method pairs every participant receiving the clinical worsening intervention with every participant not receiving the clinical worsening intervention within each stratum. Within each pairing, a +1 is assigned to the better participant, -1 to the worse participant, and 0 if they are tied. The comparison begins with ACM. Tied pairings are then compared using HFHR. Any remaining tied pairings are compared using change in HRQOL. A 'Win' represents a participant doing better within each pairing (receiving +1) based on the hierarchical comparison. The reported unit is the total wins for each intervention group from performing such a hierarchical comparison across all strata.
Time frame: 12 weeks
Population: Subjects randomized to the Clinical Worsening intervention only (n=12) + those randomized to both interventions (n=18) vs Subjects randomized to the Dietary intervention only (n=20) + those randomized to Neither intervention (n=12)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Time to All-Cause Death | 0 Total number of wins |
| Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Time to Heart-Failure Readmission | 136 Total number of wins |
| Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Change in MLHFQ from Baseline to 12 Weeks | 146 Total number of wins |
| Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Overall (across 3 outcomes) | 282 Total number of wins |
| No Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Overall (across 3 outcomes) | 219 Total number of wins |
| No Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Time to All-Cause Death | 0 Total number of wins |
| No Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Change in MLHFQ from Baseline to 12 Weeks | 63 Total number of wins |
| No Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Time to Heart-Failure Readmission | 156 Total number of wins |
Comparison: Clinical Worsening Intervention includes those in treatment group C and D. No Clinical Worsening Intervention includes those in group A and B. By the unmatched pairs win ratio method, each participant receiving the intervention will be compared to each participant not receiving the intervention. For each comparison, winners will be determined according to the hierarchy described above. The win ratio is the number winners divided by the number of losers associated with the intervention.95% CI: [1.08, 1.54]
Primary
Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ]
Time to all-cause mortality (ACM), time to heart failure hospital readmission (HFHR), and decline in quality of life will be analyzed using the Finkelstein-Schoenfeld method. The method combines these three endpoints in a hierarchical fashion using ACM first, HRHR second, and change in HRQOL third. The method pairs every participant receiving the diet intervention with every participant not receiving the diet intervention within each stratum. Within each pairing, a +1 is assigned to the better participant, -1 to the worse participant, and 0 if they are tied. The comparison begins with ACM. Tied pairings are then compared using HFHR. Any remaining tied pairings are compared using change in HRQOL. A 'Win' represents a participant doing better within each pairing (receiving +1) based on the hierarchical comparison. The reported unit is the total wins for each intervention group from performing such a hierarchical comparison across all strata.
Time frame: 12 weeks
Population: Subjects randomized to the Dietary intervention only (n=20) + those randomized to both interventions (n=18) vs Subjects randomized to the Clinical Worsening intervention only (n=12) + those randomized to Neither intervention (n=12)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Time to All-Cause Death | 0 Total number of wins |
| Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Time to Heart-Failure Readmission | 136 Total number of wins |
| Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Change in MLHFQ from Baseline to 12 Weeks | 146 Total number of wins |
| Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Overall (across 3 outcomes) | 282 Total number of wins |
| No Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Overall (across 3 outcomes) | 219 Total number of wins |
| No Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Time to All-Cause Death | 0 Total number of wins |
| No Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Change in MLHFQ from Baseline to 12 Weeks | 63 Total number of wins |
| No Dietary Sodium Intervention | Hierarchical Combination (Win Ratio) of Time to All-cause Mortality, Time to Heart Failure Hospital Readmission, and Decline in Health-related Quality of Life (HRQOL) [ Time Frame: Baseline up to Week 12 ] | Time to Heart-Failure Readmission | 156 Total number of wins |
Comparison: Dietary Sodium Intervention includes those in treatment group B and D. No Dietary Sodium Intervention includes those in treatment group A and C. By the unmatched pairs win ratio method, each participant receiving the intervention will be compared to each participant not receiving the intervention. For each comparison, winners will be determined according to the hierarchy described above. The win ratio is the number winners divided by the number of losers associated with the intervention.95% CI: [1.08, 1.54]
Secondary
All-Cause Mortality [ Time Frame: Baseline up to Week 12 ]
Time to all-cause mortality will be analyzed up to week 12.
Time frame: 12 weeks
Population: no deaths in the study and this outcome could not be assessed
Secondary
Change From Baseline in Health-related Quality of Life [ Time Frame: Baseline up to Week 12 ]
Change from baseline to week 12 in health-related quality of life as measured by the Minnesota Living with Heart Failure Questionnaire.
Time frame: 12 Weeks
Population: Subjects randomized to the Clinical Worsening intervention only (n=12) + those randomized to both interventions (n=18) vs Subjects randomized to the Dietary intervention only (n=20) + those randomized to Neither intervention (n=12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dietary Sodium Intervention | Change From Baseline in Health-related Quality of Life [ Time Frame: Baseline up to Week 12 ] | -42.29 Points on MLHFQ scale | Standard Deviation 28.169 |
| No Dietary Sodium Intervention | Change From Baseline in Health-related Quality of Life [ Time Frame: Baseline up to Week 12 ] | -29.32 Points on MLHFQ scale | Standard Deviation 34.036 |
Comparison: Clinical Worsening Intervention includes those in treatment group C and D. No Clinical Worsening Intervention includes those in treatment group A and B. Simple linear regression models will be used to assess the outcome of change in MLHFQ over 12 weeks as a function of treatment group assignment. Beta coefficients and 95% confidence intervals will be reported.95% CI: [-33.67, 7.72]
Secondary
Change From Baseline in Health-related Quality of Life [ Time Frame: Baseline up to Week 12 ]
Change from baseline to week 12 in health-related quality of life as measured by the Minnesota Living with Heart Failure Questionnaire.
Time frame: 12 weeks
Population: Subjects randomized to the Dietary intervention only (n=20) + those randomized to both interventions (n=18) vs Subjects randomized to the Clinical Worsening intervention only (n=12) + those randomized to Neither intervention (n=12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dietary Sodium Intervention | Change From Baseline in Health-related Quality of Life [ Time Frame: Baseline up to Week 12 ] | -39.70 Points on MLHFQ scale | Standard Deviation 33.908 |
| No Dietary Sodium Intervention | Change From Baseline in Health-related Quality of Life [ Time Frame: Baseline up to Week 12 ] | -24.33 Points on MLHFQ scale | Standard Deviation 24.828 |
Comparison: Dietary Sodium Intervention includes those in treatment group B and D. No Dietary Sodium Intervention includes those in treatment group A and C. Simple linear regression models will be used to assess the outcome of change in MLHFQ over 12 weeks as a function of treatment group assignment. Beta coefficients and 95% confidence intervals will be reported.95% CI: [-37.5, 6.76]
Secondary
Heart Failure-related Hospitalizations [ Time Frame: Baseline up to Week 12 ]
Time to first heart-failure related hospitalization will be analyzed up to week 12.
Time frame: 12 weeks
Population: Subjects randomized to the Dietary intervention only (n=20) + those randomized to both interventions (n=18) vs Subjects randomized to the Clinical Worsening intervention only (n=12) + those randomized to Neither intervention (n=12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dietary Sodium Intervention | Heart Failure-related Hospitalizations [ Time Frame: Baseline up to Week 12 ] | 43.4285714 Days since randomization | Standard Deviation 24.48712 |
| No Dietary Sodium Intervention | Heart Failure-related Hospitalizations [ Time Frame: Baseline up to Week 12 ] | 48.5000000 Days since randomization | Standard Deviation 19.3649167 |
Comparison: Dietary Sodium Intervention includes those in treatment group B and D. No Dietary Sodium Intervention includes those in treatment group A and C.95% CI: [0.321, 3.743]
Secondary
Heart Failure-related Hospitalizations [ Time Frame: Baseline up to Week 12 ]
Time to first heart-failure related hospitalization will be analyzed up to week 12.
Time frame: 12 weeks
Population: Subjects randomized to the Clinical Worsening intervention only (n=12) + those randomized to both interventions (n=18) vs Subjects randomized to the Dietary intervention only (n=20) + those randomized to Neither intervention (n=12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dietary Sodium Intervention | Heart Failure-related Hospitalizations [ Time Frame: Baseline up to Week 12 ] | 53.7500000 Days since randomization | Standard Deviation 14.4308697 |
| No Dietary Sodium Intervention | Heart Failure-related Hospitalizations [ Time Frame: Baseline up to Week 12 ] | 40.4285714 Days since randomization | Standard Deviation 24.8720535 |
Comparison: Clinical Worsening Intervention includes those in treatment group C and D. No Clinical Worsening Intervention includes those in treatment group A and B.95% CI: [0.163, 1.901]