HypertensionPhase 2NCT02230891
Biomarker Guided Therapies in Stage A/B Heart Failure
A Phase 2 study testing Carvedilol and Spironolactone in people with Hypertension and Diabetes, run by VA Office of Research and Development at 1 site in United States.
Trial summary
Despite advances in cardiovascular care, the occurrence of heart failure (HF) is steadily increasing. The increase in HF rates poses enormous challenges, as once an individual becomes symptomatic or requires hospitalization with HF, the prognosis remains poor. Therefore, prevention of HF is essential. Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Hypertension, Diabetes, Cardiovascular Disease
- What is being tested?
- Carvedilol and Spironolactone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2014to 15 Dec 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Only Veterans are eligible to participate. Other inclusion criteria include
- Age greater than 40 years
- One of the following in order to establish Stage A HF a. Hypertension b. Diabetes mellitus (controlled: defined as hemoglobin A1c less than 9%) c. Obesity (defined as BMI greater than 30 kg/m2) d. Metabolic syndrome (using the National Cholesterol Education Panel definition) e. Left ventricular hypertrophy (by ECG) f. Coronary or cerebrovascular arterial disease
- Troponin T measured by the high sensitivity assay of greater than 5ng/L
- Systolic BP 120-155 mmHg at primary care provider (PCP) visit and prerandomization visit (i.e., 2 separate confirmations of the same). If there is discordance between the PCP visit and pre-randomization the investigators will bring patient back to recheck his BP and use that as the tie breaker. Not orthostatic with measurements (defined as a fall in systolic BP greater than 20 mmHg when subjects assume an upright position). - Estimated 10-yr HF risk (based on Atherosclerosis Risk in Communities HF Lab model) greater than 5%
- Provides informed consent
Who cannot join
- The exclusion criteria include
- Active Atrial fibrillation
- History of chest/ neck radiation
- High-risk chronic obstructive pulmonary disease (COPD) (GOLD classification 3-4 with greater than equal to 2 COPD exacerbations in the last 12 months)
- Known allergy to carvedilol or spironolactone
- Renal insufficiency with estimated Glomerular Filtration Rate (eGFR) less than 60 ml/min
Show all 25Show fewer
- Serum potassium greater than 5 meq/L
- Current use of carvedilol, spironolactone, any other beta-blockers or aldosterone antagonists
- Signs of clinical HF on initial examination (pulmonary rales/crackles, elevated jugular venous pulse with S3/S4 on auscultation)
- Left ventricular ejection fraction <50% by echo
- Moderate or greater valve stenosis or regurgitation
- Hypertrophic cardiomyopathy
- Exposure to known cardiotoxic chemotherapy
- Poor echo image quality
- Right ventricular dysfunction more than mild
- Any valvular dysfunction that is more than mild
- Any life-threatening disease expected to result in death within the next 2 years
- Active severe liver disease (evaluated at Visit 1): cirrhosis, active hepatitis, aspartate transaminase (ALT) or alanine transaminase (AST) greater than 3 x ULN, or biliary obstruction with hyperbilirubinemia (total bilirubin greater than 2 x ULN).
- Participation in another clinical trial involving an investigational agent within 90 days prior to randomization
- Any condition or therapy which, in the opinion of the investigator, might pose a risk to the patient or make participation in the study not in the patient s best interest
- Drug or alcohol abuse within the past 6 months, and unable/unwilling to abstain from drug abuse and excessive alcohol consumption during the study. Excessive alcohol consumption is on average greater than 2 units of alcohol per day. A unit of alcohol is defined as a 12-ounce (350 mL) beer, 5-ounce (150 mL) wine, or 1.5-ounce (45 mL) of 80 ]proof alcohol for drinks.
- Mental/psychological impairment or any other reason to expect patient difficulty in complying with the requirements of the study.
- Any immunosuppressed condition where intercurrent illnesses may affect interpretation of study results
- Pregnant women or any woman planning a pregnancy during the study period
- Not meeting any of the inclusion criteria
Trial locations and contacts
1 site in 1 country.
United States1 site
Michael E. DeBakey VA Medical Center, Houston, TX
Houston, Texas, 77030
About this study
Despite advances in cardiovascular care, the occurrence of heart failure (HF) is steadily increasing. The increase in HF rates poses enormous challenges, as once an individual becomes symptomatic or requires hospitalization with HF, the prognosis remains poor. Therefore, prevention of HF is essential. HF prevention is a critical issue as HF risk factors that include common medical conditions such as hypertension and diabetes are also increasing. However, not everyone with these risk factors develops HF. Using novel blood tests, the investigators propose to identify and treat subjects at higher HF risk to see if the investigators can stabilize or improve ultrasound measures known to be associated with HF risk. This study will enroll only Veterans.
Read the detailed description
Recently the investigators have shown that HF risk prediction can be improved using cardiac troponin T measured with a novel high-sensitivity assay (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Furthermore, hs-cTnT seems to identify individuals at higher risk among those with established risk factors (such as hypertension) for HF. In preliminary results, the investigators have shown that individuals with systolic blood pressure of 120-129 mm Hg and elevated hs-cTnT have a higher rate of incident HF than those with systolic blood pressure of 140-159 mm Hg and undetectable hs-cTnT. Therefore, the investigators believe that by using hs-cTnT to estimate HF risk the investigators can identify individuals in whom aggressive modification of risk factors such as high blood pressure will be associated with a favorable risk-benefit ratio.
The investigators' objective/specific aim therefore is to evaluate if treatment of selected subjects with Stage A or B HF (i.e., those with hs-cTnT >5 ng/L and an estimated 10-year HF hospitalization risk of >5%) who have reasonably well-controlled blood pressure with antihypertensive agents (carvedilol or spironolactone) will be associated with improvement of surrogate markers associated with incident HF (i.e., speckle-tracked cardiac and vascular strain). Carvedilol and spironolactone were chosen for the following reasons: a) they are not routinely used as first-line antihypertensive agents; b) beta-blockade was associated with decreases in hs-cTnT in the preliminary analysis of subjects with established HF; and c) the mechanism of actions of carvedilol and spironolactone provide a sound scientific rationale for use in prevention of HF.
Using a prospective open-label blinded end point (PROBE) design, the investigators propose to randomize 210 subjects aged >40 years with systolic blood pressure between 120-155 mm Hg, cardiac troponin T (measured with a novel high-sensitivity assay) level >5 ng/L, and 10-year HF risk >5% (estimated using a validated laboratory model including demographic factors, NT-proBNP, and hs-cTnT) to receive carvedilol (nonselective beta-blocker), spironolactone (aldosterone antagonist), or usual care for 18 months. The primary end point will be change in global longitudinal systolic myocardial strain estimated using 2D speckle tracking. Additionally, changes in vascular strain and biomarkers will be evaluated. This study will help us identify whether both or either of the medications can be further tested in large randomized clinical trials to prevent the incidence of HF.
- Conditions
- Hypertension, Diabetes, Cardiovascular Disease
- Being tested
- Carvedilol, Spironolactone, Usual care
- Keywords
- heart failure, biomarkers, troponin, BNP, carvedilol, spironolactone, prevention
- Medical subject headings
- Hypertension, Diabetes Mellitus, Cardiovascular Diseases, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
Carvedilol is a non selective beta blocker
SpironolactoneDrug
Spironolactone is an aldosterone antagonist and can lower blood pressure/ is used in heart failure
Usual careOther
standard care as per primary care provider
| Study group | Role | What they receive |
|---|---|---|
| Carvedilol | Active comparator | Approximately 70 subjects will be randomized to carvedilol Receives: Drug: Carvedilol |
| Spironolactone | Active comparator | Approximately 70 subjects will be randomized to spironolactone Receives: Drug: Spironolactone |
| Usual care | Other | Approximately 70 subjects will be randomized to usual care/ standard care by primary care providers Receives: Other: Usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cardiac Global Longitudinal Strain
Change in myocardial speckle tracked strain (global longitudinal strain) after 18 months (baseline vs. 18 months) of therapy with carvedilol or spironolactone or usual care. The myocardial global longitudinal strain was measured using echocardiography
Measured: 18 months
Secondary outcomes (3)
Change in NTproBNP (Biomarker)
Change in levels of NT-proBNP (measured in blood samples) between baseline and 18 months after therapy with carvedilol or spironolactone or usual care
Measured: 18 months
Change in Pulse Wave Velocity
Changes in arterial stiffness between baseline and 18 months after therapy with carvedilol, spironolactone or usual care. Arterial stiffness was measured by pulse wave velocity (Sphygmocor device)
Measured: 18 months
Change in Troponin T Measured Using a High Sensitivity Assay
Change in levels of troponin T (measured with a high sensitivity assay in blood samples) between baseline and 18 months after therapy with carvedilol or spironolactone or usual care
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2014 (estimated)
- Study start1 Oct 2014
- Primary completion15 Dec 2020
- Study completion15 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- Baylor College of Medicine
- Responsible party
- Sponsor
- Investigators
- Vijay Nambi, MBBS, Principal investigator, Michael E. DeBakey VA Medical Center, Houston, TX
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02230891
- Sponsor's protocol ID
- CLNB-009-13F
- Status last verified
- Oct 2022
- First submitted
- 28 Aug 2014
- Last updated
- 21 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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 21 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarker Guided Therapies in Stage A/B Heart Failure
- ClinicalTrials.gov ID
- NCT02230891
- Acronym / sponsor ID
- CLNB-009-13F
- Conditions
- Hypertension, Diabetes, Cardiovascular Disease
- Keywords
- heart failure, biomarkers, troponin, BNP, carvedilol, spironolactone, prevention
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- Baylor College of Medicine
- Study start
- 1 Oct 2014 (actual)
- Primary completion
- 15 Dec 2020 (actual)
- Study completion
- 15 Dec 2020 (actual)
- First posted
- 3 Sep 2014 (estimated)
- Results
- Posted 29 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Despite advances in cardiovascular care, the occurrence of heart failure (HF) is steadily increasing. The increase in HF rates poses enormous challenges, as once an individual becomes symptomatic or requires hospitalization with HF, the prognosis remains poor. Therefore, prevention of HF is essential. HF prevention is a critical issue as HF risk factors that include common medical conditions such as hypertension and diabetes are also increasing. However, not everyone with these risk factors develops HF. Using novel blood tests, the investigators propose to identify and treat subjects at higher HF risk to see if the investigators can stabilize or improve ultrasound measures known to be associated with HF risk. This study will enroll only Veterans.
Detailed description
Recently the investigators have shown that HF risk prediction can be improved using cardiac troponin T measured with a novel high-sensitivity assay (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Furthermore, hs-cTnT seems to identify individuals at higher risk among those with established risk factors (such as hypertension) for HF. In preliminary results, the investigators have shown that individuals with systolic blood pressure of 120-129 mm Hg and elevated hs-cTnT have a higher rate of incident HF than those with systolic blood pressure of 140-159 mm Hg and undetectable hs-cTnT. Therefore, the investigators believe that by using hs-cTnT to estimate HF risk the investigators can identify individuals in whom aggressive modification of risk factors such as high blood pressure will be associated with a favorable risk-benefit ratio.
The investigators' objective/specific aim therefore is to evaluate if treatment of selected subjects with Stage A or B HF (i.e., those with hs-cTnT >5 ng/L and an estimated 10-year HF hospitalization risk of >5%) who have reasonably well-controlled blood pressure with antihypertensive agents (carvedilol or spironolactone) will be associated with improvement of surrogate markers associated with incident HF (i.e., speckle-tracked cardiac and vascular strain). Carvedilol and spironolactone were chosen for the following reasons: a) they are not routinely used as first-line antihypertensive agents; b) beta-blockade was associated with decreases in hs-cTnT in the preliminary analysis of subjects with established HF; and c) the mechanism of actions of carvedilol and spironolactone provide a sound scientific rationale for use in prevention of HF.
Using a prospective open-label blinded end point (PROBE) design, the investigators propose to randomize 210 subjects aged >40 years with systolic blood pressure between 120-155 mm Hg, cardiac troponin T (measured with a novel high-sensitivity assay) level >5 ng/L, and 10-year HF risk >5% (estimated using a validated laboratory model including demographic factors, NT-proBNP, and hs-cTnT) to receive carvedilol (nonselective beta-blocker), spironolactone (aldosterone antagonist), or usual care for 18 months. The primary end point will be change in global longitudinal systolic myocardial strain estimated using 2D speckle tracking. Additionally, changes in vascular strain and biomarkers will be evaluated. This study will help us identify whether both or either of the medications can be further tested in large randomized clinical trials to prevent the incidence of HF.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Carvedilol | Active comparator | Drug: CarvedilolApproximately 70 subjects will be randomized to carvedilol |
| Spironolactone | Active comparator | Drug: SpironolactoneApproximately 70 subjects will be randomized to spironolactone |
| Usual care | Other | Other: Usual careApproximately 70 subjects will be randomized to usual care/ standard care by primary care providers |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Only Veterans are eligible to participate. Other inclusion criteria include
- Age greater than 40 years
- One of the following in order to establish Stage A HF a. Hypertension b. Diabetes mellitus (controlled: defined as hemoglobin A1c less than 9%) c. Obesity (defined as BMI greater than 30 kg/m2) d. Metabolic syndrome (using the National Cholesterol Education Panel definition) e. Left ventricular hypertrophy (by ECG) f. Coronary or cerebrovascular arterial disease
- Troponin T measured by the high sensitivity assay of greater than 5ng/L
- Systolic BP 120-155 mmHg at primary care provider (PCP) visit and prerandomization visit (i.e., 2 separate confirmations of the same). If there is discordance between the PCP visit and pre-randomization the investigators will bring patient back to recheck his BP and use that as the tie breaker. Not orthostatic with measurements (defined as a fall in systolic BP greater than 20 mmHg when subjects assume an upright position). - Estimated 10-yr HF risk (based on Atherosclerosis Risk in Communities HF Lab model) greater than 5%
Key exclusion criteria (25 listed)
- The exclusion criteria include
- Active Atrial fibrillation
- History of chest/ neck radiation
- High-risk chronic obstructive pulmonary disease (COPD) (GOLD classification 3-4 with greater than equal to 2 COPD exacerbations in the last 12 months)
- Known allergy to carvedilol or spironolactone
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 |
|---|---|---|
| CarvedilolCarvedilol is a non selective beta blocker | Drug | Carvedilol |
| SpironolactoneSpironolactone is an aldosterone antagonist and can lower blood pressure/ is used in heart failure | Drug | Spironolactone |
| Usual carestandard care as per primary care provider | Other | Usual care |
Primary outcome
Change in Cardiac Global Longitudinal Strain
Time frame: 18 months
Change in myocardial speckle tracked strain (global longitudinal strain) after 18 months (baseline vs. 18 months) of therapy with carvedilol or spironolactone or usual care. The myocardial global longitudinal strain was measured using echocardiography
3 secondary outcomes
Change in NTproBNP (Biomarker)
Time frame: 18 months
Change in Pulse Wave Velocity
Time frame: 18 months
Change in Troponin T Measured Using a High Sensitivity Assay
Time frame: 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Hypertension
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Enrolling by invitation
Testing Implementation Strategies to Support Clinic Fidelity to an Outpatient Hypertension Bundle
Pregnancy Related, Hypertension
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.
Vijay Nambi, MBBS principal investigator
Michael E. DeBakey VA Medical Center, Houston, TX
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carvedilol and Spironolactone in people with Hypertension and Diabetes, run by VA Office of Research and Development 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 6 inclusion and 25 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 21 Oct 2022. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Cardiac Global Longitudinal Strain (time frame: 18 months). 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 21 Oct 2022.