Heart Failure, SystolicNCT04743063
Prospective Monitoring of Angiotensin Receptor Neprilysin Inhibitor in Older Adults With Heart Failure and Frailty
An observational study of Heart Failure, Systolic and Frailty, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
The objective of this study is to establish a near-real-time prospective monitoring program in Medicare, Optum and MarketScan Research data to evaluate the benefit of new cardiovascular disease (CVD) drugs for older adults with frailty. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Heart Failure, Systolic, Frailty
- What is being tested?
- sacubitril/valsartan and Angiotensin II Receptor Blockers
- How many people
- 40,000 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jan 2021to 31 Dec 2022
- 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Study population: Study population includes older patients with heart failure with reduced ejection fraction who initiates an angiotensin receptor neprilysin inhibitor or an angiotensin II receptor blocker.
Who may be able to join
- Continuous enrollment for medical and drug insurance (e.g., Medicare Part A, B, and D) in [-365, 0] days
- Diagnosis of Heart Failure either two outpatient diagnosis or one inpatient diagnosis in [-365, 0] days
- Reduced Ejection Fraction < 45% identified using a validated claims-based algorithm in [-365, 0] days
- Day 0 is the initiation date of the study drug.
Who cannot join
- No prior use of Angiotensin receptor neprilysin inhibitor or angiotensin II receptor blocker in [-365, -1] days
- No recent HF hospitalization, defined as HF diagnosis (defined in attached protocol) in the primary position in the inpatient dataset in [-60, 0] days
- No recent nursing facility stay (defined in attached protocol) for [-60, 0] days
- Age < 65 years
- Exposure to both drugs on day 0
- Contraindication to either drug (exclusion assessment window: [-60, 0] days, unless specified otherwise; algorithms specified in attached protocol)
- Note: If a patient meets the above-mentioned eligibility criteria more than once, only the first record will be included.
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham And Women's Hospital
Boston, Massachusetts, 02120
About this study
The objective of this study is to establish a near-real-time prospective monitoring program in Medicare, Optum and MarketScan Research data to evaluate the benefit of new cardiovascular disease (CVD) drugs for older adults with frailty. Prospective monitoring program seeks to find early effectiveness and safety signals of new drugs by updating the analysis at regular intervals as new Medicare data become available. This study specifically aims to emulate a prospective surveillance of the effectiveness and safety of Angiotensin Receptor Neprilysin Inhibitor(ARNI) vs. a comparator, Angiotensin II Receptor Blockers (ARBs), in older adults with Heart Failure with Reduced Ejection Fraction (HFrEF) and different frailty status. This program will be enhanced by incorporating a novel claims-based frailty index, which has been shown useful in assessing how the benefits and harms of drug therapy vary by frailty.
Read the detailed description
Data sources of use for this study are: Medicare Database, Optum Database, and MarketScan Research Database. All data from years 2014-2020 will be included in the study.
This study follows a sequential cohort monitoring design. The monitoring analysis will include 1) retrospective analysis of available data (2015-2017) at the time of first analysis (January 2021) and 2) prospective analysis of new data (2018-2020) as they become available to the researchers. Within each database, we will emulate biannual updating of data by creating a propensity score (PS)-matched cohort of new users every 6-month interval, beginning on the first marketing of ARNI (July 7, 2015-December 31, 2015, and 6-month intervals afterwards). Each sequential cohort will be followed for development of the outcomes of interest. Outcome analysis will be performed at a pre-specified 6-month interval (prospective analysis). The surveillance will be performed by frailty status (frail vs non-frail) at the time of drug initiation. The results from each database will be pooled using fixed-effects meta-analysis (assuming low heterogeneity across the databases).
- Conditions
- Heart Failure, Systolic, Frailty
- Being tested
- sacubitril/valsartan, Angiotensin II Receptor Blockers
- Medical subject headings
- Heart Failure, Systolic, Frailty
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sacubitril/valsartanDrug
Initiation of sacubitril/valsartan, identified using prescription fill in pharmacy claims
Angiotensin II Receptor BlockersDrug
Also called azilsartan, candesartan, eprosartan, Irbesartan
Initiation of ARBs, identified using prescription fill in pharmacy claims
| Study group | Role | What they receive |
|---|---|---|
| New users of angiotensin receptor neprilysin inhibitor | Not described Receives: Drug: sacubitril/valsartan | |
| New users of angiotensin II receptor blockers | Not described Receives: Drug: Angiotensin II Receptor Blockers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with composite events of death or heart failure hospitalization
All-cause mortality OR heart failure hospitalization
Measured: July 2015 - December 2020
Number of patients with composite serious adverse events
Hypotension OR acute kidney injury/acute kidney failure OR hyperkalemia OR angioedema
Measured: July 2015 - December 2020
Secondary outcomes (6)
Number of patients with all-cause mortality
All-cause mortality is defined by the National Death Index file or vital status information in the claims dataset.
Measured: July 2015 - December 2020
Number of patients with heart failure hospitalization
Heart failure hospitalization is defined as any hospitalization with relevant diagnosis codes in the primary position.
Measured: July 2015 - December 2020
Number of patients with hypotension
Hypotension is defined as any hospitalization or Emergency Department visit with relevant diagnosis codes in the primary position.
Measured: July 2015 - December 2020
Number of patients with hyperkalemia
Hyperkalemia is defined as any hospitalization or Emergency Department visit with relevant diagnosis codes in the primary position.
Measured: July 2015 - December 2020
Number of patients with acute kidney injury/acute kidney failure
Acute kidney injury/Acute kidney failure is defined as any hospitalization or Emergency Department visit with relevant diagnosis codes in the primary position.
Measured: July 2015 - December 2020
Number of patients with angioedema
Angioedema is defined as any hospitalization or Emergency Department visit with relevant diagnosis codes in the primary position.
Measured: July 2015 - December 2020
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2021
- Study start14 Jan 2021
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure, SystolicStudies 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
- 40,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dae Hyun Kim, MD, MPH, ScD, Brigham and Women's Hospital
- Investigators
- Dae Hyun Kim, MD, MPH, ScD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04743063
- Sponsor's protocol ID
- 2019P000110-ARNI
- Status last verified
- Feb 2021
- First submitted
- 3 Feb 2021
- Last updated
- 15 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Monitoring of Angiotensin Receptor Neprilysin Inhibitor in Older Adults With Heart Failure and Frailty
- ClinicalTrials.gov ID
- NCT04743063
- Acronym / sponsor ID
- 2019P000110-ARNI
- Conditions
- Heart Failure, Systolic, Frailty
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40,000 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 14 Jan 2021 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 8 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.
The objective of this study is to establish a near-real-time prospective monitoring program in Medicare, Optum and MarketScan Research data to evaluate the benefit of new cardiovascular disease (CVD) drugs for older adults with frailty. Prospective monitoring program seeks to find early effectiveness and safety signals of new drugs by updating the analysis at regular intervals as new Medicare data become available. This study specifically aims to emulate a prospective surveillance of the effectiveness and safety of Angiotensin Receptor Neprilysin Inhibitor(ARNI) vs. a comparator, Angiotensin II Receptor Blockers (ARBs), in older adults with Heart Failure with Reduced Ejection Fraction (HFrEF) and different frailty status. This program will be enhanced by incorporating a novel claims-based frailty index, which has been shown useful in assessing how the benefits and harms of drug therapy vary by frailty.
Detailed description
Data sources of use for this study are: Medicare Database, Optum Database, and MarketScan Research Database. All data from years 2014-2020 will be included in the study.
This study follows a sequential cohort monitoring design. The monitoring analysis will include 1) retrospective analysis of available data (2015-2017) at the time of first analysis (January 2021) and 2) prospective analysis of new data (2018-2020) as they become available to the researchers. Within each database, we will emulate biannual updating of data by creating a propensity score (PS)-matched cohort of new users every 6-month interval, beginning on the first marketing of ARNI (July 7, 2015-December 31, 2015, and 6-month intervals afterwards). Each sequential cohort will be followed for development of the outcomes of interest. Outcome analysis will be performed at a pre-specified 6-month interval (prospective analysis). The surveillance will be performed by frailty status (frail vs non-frail) at the time of drug initiation. The results from each database will be pooled using fixed-effects meta-analysis (assuming low heterogeneity across the databases).
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| New users of angiotensin receptor neprilysin inhibitor | – | Drug: sacubitril/valsartan |
| New users of angiotensin II receptor blockers | – | Drug: Angiotensin II Receptor Blockers |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
- Study population
- Study population includes older patients with heart failure with reduced ejection fraction who initiates an angiotensin receptor neprilysin inhibitor or an angiotensin II receptor blocker.
Key inclusion criteria (4 listed)
- Continuous enrollment for medical and drug insurance (e.g., Medicare Part A, B, and D) in [-365, 0] days
- Diagnosis of Heart Failure either two outpatient diagnosis or one inpatient diagnosis in [-365, 0] days
- Reduced Ejection Fraction < 45% identified using a validated claims-based algorithm in [-365, 0] days
Key exclusion criteria (7 listed)
- No prior use of Angiotensin receptor neprilysin inhibitor or angiotensin II receptor blocker in [-365, -1] days
- No recent HF hospitalization, defined as HF diagnosis (defined in attached protocol) in the primary position in the inpatient dataset in [-60, 0] days
- No recent nursing facility stay (defined in attached protocol) for [-60, 0] days
- Age < 65 years
- Exposure to both drugs on day 0
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 |
|---|---|---|
| sacubitril/valsartanInitiation of sacubitril/valsartan, identified using prescription fill in pharmacy claims | Drug | New users of angiotensin receptor neprilysin inhibitor |
| Angiotensin II Receptor BlockersAlso: azilsartan, candesartan, eprosartan, IrbesartanInitiation of ARBs, identified using prescription fill in pharmacy claims | Drug | New users of angiotensin II receptor blockers |
Primary outcome
Number of patients with composite events of death or heart failure hospitalization
Time frame: July 2015 - December 2020
All-cause mortality OR heart failure hospitalization
Number of patients with composite serious adverse events
Time frame: July 2015 - December 2020
Hypotension OR acute kidney injury/acute kidney failure OR hyperkalemia OR angioedema
6 secondary outcomes
Number of patients with all-cause mortality
Time frame: July 2015 - December 2020
Number of patients with heart failure hospitalization
Time frame: July 2015 - December 2020
Number of patients with hypotension
Time frame: July 2015 - December 2020
Number of patients with hyperkalemia
Time frame: July 2015 - December 2020
Number of patients with acute kidney injury/acute kidney failure
Time frame: July 2015 - December 2020
Number of patients with angioedema
Time frame: July 2015 - December 2020
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2021.
- Individual participant dataSharing planned: No
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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.
Dae Hyun Kim, MD, MPH, ScD 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, Systolic and Frailty, 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 4 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 15 Feb 2021. 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?
Results are not available in the source record.
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?
Number of patients with composite events of death or heart failure hospitalization (time frame: July 2015 - December 2020). The study lists 2 primary outcomes in all. 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 15 Feb 2021.