Heart FailureNCT04736433
Replication of the PARADIGM-HF Heart Failure Trial in Healthcare Claims Data.
An observational study of Heart Failure, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- ACE inhibitor and Sacubitril/Valsartan
- How many people
- 6,066 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Sep 2020to 18 Feb 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Adult, Older adult
Study population: This study will involve a new user, parallel group retrospective cohort study design comparing sacubitril/valsartan to ACE inhibitors. Although the trial compared sacubitril/valsartan to enalapril, we expanded the definition of the comparator group to include all ACEi therapies to improve power, since all medications within this class of medication are indicated and guideline recommended for use in heart failure with reduced ejection fraction patients and would be expected to have similar effects on the primary outcome of CV death and HF hospitalization. The patients will be required to have continuous enrollment during the baseline period of 180 days before initiation of sacubitril/valsartan or a ACEi (cohort entry).
Who may be able to join
- Age 18 years or older
- NYHA functional class II-IV
- LVEF ≤ 35%
- AND the following:
- Hospitalization for heart failure within the last 12 months
- Treatment with a stable dose of an ACE inhibitor or an ARB equivalent to enalapril 10 mg/day for at least 4 weeks before the screening visit; and treatment with a stable dose of a beta-blocker for at least 4 weeks prior to the screening visit, unless contraindicted or not tolerated
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- Treatment with a stable dose of an ACE inhibitor or an ARB equivalent to enalapril 10 mg/day for at least 4 weeks before the screening visit
- AND the following:
- Treatment with a stable dose of a beta-blocker for at least 4 weeks prior to the screening visit, unless contraindicated or not tolerated
Who cannot join
- Known history of angioedema
- Requirement for treatment with both ACEIs and ARBs
- Current acute decompensated heart failure (exacerbation of chronic heart failure manifested by signs and symptoms that may require intravenous therapy)
- Symptomatic hypotension and/or a systolic blood pressure <100 mmHg at Visit 1 (screening) or <95 mmHg at Visit 3 or at Visit 5 (randomization)
- Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 at Visit 1 (screening), Visit 3 (end of enalapril run-in), or Visit 5 (end of LCZ696 run-in and randomization) or >35% decline in eGFR between Visit 1 and Visit 3 or between Visit 1 and Visit 5
- Serum potassium >5.2 mmol/L at Visit 1 (screening) or >5.4 mmol/L at Visit 3 or Visit 5 (randomization)
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- Acute coronary syndrome, stroke, transient ischaemic attack, cardiac, carotid, or other major cardiovascular surgery, PCI, or carotid angioplasty within the 3 months prior to Visit 1.
- Implantation of a cardiac resynchronization therapy (CRT) device within 3 months prior Visit 1 or intent to implant a CRT
- History of heart transplant or on a transplant list or with LV assistance device
- History of severe pulmonary disease
- Diagnosis of peripartum- or chemotherapy-induced cardiomyopathy within the 12 months prior to Visit 1
- Documented untreated ventricular arrhythmia with syncopal episodes within the 3 months prior to Visit 1
- Documented ventricular arrhythmia within the 3 months prior to Visit 1
- AND the following:
- Syncopal episodes within the 3 months prior to Visit 1
- AND the following:
- Untreated ventricular arrhythmia within the 3 months prior to visit 1
- OR the following:
- Untreated ventricular arrhythmia within the 3 months prior to visit 1
- Symptomatic bradycardia or second- or third-degree atrioventricular block without a pacemaker
- Presence of haemodynamically significant mitral and/or aortic valve disease, except mitral regurgitation secondary to LV dilatation
- Presence of other haemodynamically significant obstructive lesions of the LV outflow tract, including aortic and subaortic stenosis
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs, including, but not limited to, any of the following:
- History of active inflammatory bowel disease during the 12 months before Visit 1
- OR the following:
- Active duodenal or gastric ulcers during the 3 months prior to Visit 1
- OR the following:
- Evidence of hepatic disease as determined by any one of the following: aspartate aminotransferase or alanine aminotransferase values exceeding 2× upper limit of normal at Visit 1, history of hepatic encephalopathy, history of oesophageal varices, or history of porto-caval shunt
- OR the following:
- Current treatment with cholestyramine or colestipol resins
- Presence of any other disease with a life expectancy of 5 years
- Any Ivabradine use -- Approved in April 2015 (same year as Entresto)
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02120
About this study
Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
Read the detailed description
This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.
- Conditions
- Heart Failure
- Being tested
- ACE inhibitor, Sacubitril/Valsartan
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACE inhibitorDrug
ACE inhibitor dispensing claim is used as the reference
Sacubitril/ValsartanDrug
Sacubitril/Valsartan dispensing claim is used as the reference
| Study group | Role | What they receive |
|---|---|---|
| ACE Inhibitors | Reference group Receives: Drug: ACE inhibitor | |
| Sacubitril/Valsartan | Exposure group Receives: Drug: Sacubitril/Valsartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite outcome of death from cardiovascular causes or hospitalization for heart failure
Measured: Through study completion (a median of 102-139 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2021
- Study start22 Sep 2020
- Primary completion18 Feb 2021
- Study completion18 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 6,066 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shirley Vichy Wang, Brigham and Women's Hospital
- Investigators
- Shirley Wang, PhD, ScM, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04736433
- Sponsor's protocol ID
- 2018P002966-DUP-PARADIGM-HF
- Status last verified
- Jul 2023
- First submitted
- 25 Jan 2021
- Last updated
- 1 Aug 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Replication of the PARADIGM-HF Heart Failure Trial in Healthcare Claims Data.
- ClinicalTrials.gov ID
- NCT04736433
- Acronym / sponsor ID
- 2018P002966-DUP-PARADIGM-HF
- Conditions
- Heart Failure
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 6,066 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 22 Sep 2020 (actual)
- Primary completion
- 18 Feb 2021 (actual)
- Study completion
- 18 Feb 2021 (actual)
- First posted
- 3 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
Detailed description
This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ACE Inhibitors | – | Drug: ACE inhibitorReference group |
| Sacubitril/Valsartan | – | Drug: Sacubitril/ValsartanExposure group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- This study will involve a new user, parallel group retrospective cohort study design comparing sacubitril/valsartan to ACE inhibitors. Although the trial compared sacubitril/valsartan to enalapril, we expanded the definition of the comparator group to include all ACEi therapies to improve power, since all medications within this class of medication are indicated and guideline recommended for use in heart failure with reduced ejection fraction patients and would be expected to have similar effects on the primary outcome of CV death and HF hospitalization. The patients will be required to have continuous enrollment during the baseline period of 180 days before initiation of sacubitril/valsartan or a ACEi (cohort entry).
Key inclusion criteria (9 listed)
- Age 18 years or older
- NYHA functional class II-IV
- LVEF ≤ 35%
- Hospitalization for heart failure within the last 12 months
- Treatment with a stable dose of an ACE inhibitor or an ARB equivalent to enalapril 10 mg/day for at least 4 weeks before the screening visit
Key exclusion criteria (32 listed)
- Known history of angioedema
- Requirement for treatment with both ACEIs and ARBs
- Current acute decompensated heart failure (exacerbation of chronic heart failure manifested by signs and symptoms that may require intravenous therapy)
- Symptomatic hypotension and/or a systolic blood pressure <100 mmHg at Visit 1 (screening) or <95 mmHg at Visit 3 or at Visit 5 (randomization)
- Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 at Visit 1 (screening), Visit 3 (end of enalapril run-in), or Visit 5 (end of LCZ696 run-in and randomization) or >35% decline in eGFR between Visit 1 and Visit 3 or between Visit 1 and Visit 5
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ACE inhibitorACE inhibitor dispensing claim is used as the reference | Drug | ACE Inhibitors |
| Sacubitril/ValsartanSacubitril/Valsartan dispensing claim is used as the reference | Drug | Sacubitril/Valsartan |
Primary outcome
Composite outcome of death from cardiovascular causes or hospitalization for heart failure
Time frame: Through study completion (a median of 102-139 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shirley Wang, PhD, ScM principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Failure, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite outcome of death from cardiovascular causes or hospitalization for heart failure (time frame: Through study completion (a median of 102-139 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2023.