Heart Failure NYHA Class IPhase 2NCT03005184
Mechanism(s) Underlying Cardiovascular Effects of ARB/NEP Inhibition - Aim 2
A Phase 2 study testing Valsartan 80 mg bid, Enalapril 10 mg bid and Sacubitril-Valsartan 200 mg bid in people with Heart Failure NYHA Class I and Heart Failure NYHA Class II, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
This study tests the hypothesis that endogenous bradykinin contributes to effects of a combined angiotensin receptor blocker/neprilysin inhibitor (LCZ696 or Entresto) Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Heart Failure NYHA Class I, Heart Failure NYHA Class II, Heart Failure NYHA Class III
- What is being tested?
- Valsartan 80 mg bid, Enalapril 10 mg bid and Sacubitril-Valsartan 200 mg bid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2017to Jan 2020
- Phase
- Phase 2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Stable patients with a reduced EF
- EF less than or equal to 40% (confirmed by echocardiogram within the last six months), and
- history of symptoms of New York Heart Association class I, II or III HF
- stable clinical symptoms including no hospitalizations for the last six months
- treatment with a stable dose of an ACEi or ARB and with a beta blocker (unless contraindicated or not tolerated) for at least four weeks
- treatment with a stable dose of an MR antagonist for at least four weeks unless not possible due to renal function or serum potassium.
Show all 9Show fewer
- For female subjects, the following conditions must be met:
- postmenopausal status for at least one year, or
- status post-surgical sterilization
Who cannot join
- History of hypersensitivity or allergy to any of the study drugs, drugs of similar chemical classes, ACEi, ARBs, or NEPi, as well as known or suspected contraindications to the study drugs
- History of angioedema
- History of pancreatitis or known pancreatic lesions
- History of decompensated HF within the last six months (exacerbation of chronic HF manifested by signs and symptoms that required intravenous therapy or hospitalization)
- History of heart transplant or on a transplant list or with left ventricular assistance device
- Symptomatic hypotension and/or a SBP<100 mmHg at screening or <90 mmHg during the study
Show all 33Show fewer
- Serum potassium >5.2 mmol/L at screening or >5.4 mmol/L during the study
- Acute coronary syndrome, cardiac, carotid, or other major cardiovascular surgery, percutaneous coronary intervention, or carotid angioplasty within six months prior to screening
- Coronary or carotid artery disease likely to require surgical or percutaneous intervention within six months of screening
- History of serious neurologic disease such as cerebral hemorrhage, stroke, seizure, or transient ischemic attack within six months
- History of ventricular arrhythmia with syncopal episodes
- Symptomatic bradycardia or second- or third-degree atrioventricular block without a pacemaker
- Presence of hemodynamically significant mitral and/or aortic valve disease, except mitral regurgitation secondary to LV dilatation
- Presence of other hemodynamically significant obstructive lesions of the left ventricular outflow tract, including aortic and subaortic stenosis
- Type 1 diabetes
- Poorly controlled type 2 diabetes mellitus (T2DM), defined as a HgbA1c >9%
- Hematocrit <35%
- Impaired renal function (eGFR of <30mL/min/1.73 m2) as determined by the four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum creatinine (Scr) is expressed in mg/dL and age in years:
- eGFR (mL/min/1.73m2)=175 • Scr-1.154 • age-0.203 • (1.212 if Black) • (0.742 if female)
- Use of hormone-replacement therapy
- Breast feeding and pregnancy
- History or presence of immunological or hematological disorders
- History of malignancy other than non-melanoma skin cancer
- Diagnosis of asthma requiring use of inhaled beta agonist more than once a week
- Clinically significant gastrointestinal impairment that could interfere with drug absorption
- Impaired hepatic function [aspartate amino transaminase (AST) and/or alanine amino transaminase (ALT) >3.0 x upper limit of normal range]
- Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult, such as arthritis treated with non-steroidal anti-inflammatory drugs
- Treatment with chronic systemic glucocorticoid therapy within the last year
- Treatment with lithium salts
- History of alcohol or drug abuse
- Treatment with any investigational drug in the one month preceding the study
- Mental conditions rendering the subject unable to understand the nature, scope, and possible consequences of the study
- Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
This study tests the hypothesis that endogenous bradykinin contributes to effects of a combined angiotensin receptor blocker/neprilysin inhibitor (LCZ696 or Entresto)
Read the detailed description
Patients with heart failure (HF) with reduced ejection fraction who qualify for the study will undergo a three-week run-in period in which any prior angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker they were taking will be discontinued and they will be given valsartan 80 mg bid in a single-blind fashion. After the run-in, subjects will undergo four study periods in random order. During two study periods they will receive enalapril 10 mg bid and during two they will receive sacubitril/valsartan (LCZ696) 200 mg bid for seven days. On the seventh day or each period, subjects will complete a study day in which they are randomized to receive either the bradykinin B2 receptor blocker icatibant or placebo intravenously. Each study period will be separated by a three-week washout during which subjects receive valsartan 80 mg bid.
- Being tested
- Valsartan 80 mg bid, Enalapril 10 mg bid, Sacubitril-Valsartan 200 mg bid, Icatibant, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Valsartan 80 mg bidDrug
oral medication during run-in and washout period
Enalapril 10 mg bidDrug
oral medication
Sacubitril-Valsartan 200 mg bidDrug
oral medication
IcatibantDrug
intravenous medication
PlaceboDrug
intravenous medication
| Study group | Role | What they receive |
|---|---|---|
| S/V+Pla, S/V+I, Enal+Pla, Enal+I | Experimental | Enal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. Receives: Drug: Valsartan 80 mg bid; Drug: Enalapril 10 mg bid; Drug: Sacubitril-Valsartan 200 mg bid; Drug: Icatibant; Drug: Placebo |
| S/V+Pla, Enal+I, S/V+I, Enal+Pla | Experimental | Enal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. Receives: Drug: Valsartan 80 mg bid; Drug: Enalapril 10 mg bid; Drug: Sacubitril-Valsartan 200 mg bid; Drug: Icatibant; Drug: Placebo |
| S/V+Pla, Enal+Pla, Enal+I, S/V+I | Experimental | Enal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. Receives: Drug: Valsartan 80 mg bid; Drug: Enalapril 10 mg bid; Drug: Sacubitril-Valsartan 200 mg bid; Drug: Icatibant; Drug: Placebo |
| S/V+I, S/V+Pla, Enal+I, Enal+P | Experimental | Enal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. Receives: Drug: Valsartan 80 mg bid; Drug: Enalapril 10 mg bid; Drug: Sacubitril-Valsartan 200 mg bid; Drug: Icatibant; Drug: Placebo |
| S/V+I, Enal+Pla, S/V+Pla, Enal+I | Experimental | Enal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. Receives: Drug: Valsartan 80 mg bid; Drug: Enalapril 10 mg bid; Drug: Sacubitril-Valsartan 200 mg bid; Drug: Icatibant; Drug: Placebo |
| S/V+I, Enal+I, Enal+Pla, S/V+Pla | Experimental | Enal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. Receives: Drug: Valsartan 80 mg bid; Drug: Enalapril 10 mg bid; Drug: Sacubitril-Valsartan 200 mg bid; Drug: Icatibant; Drug: Placebo |
| Enal+Pla, S/V+Pla, S/V+I, Enal+I | Experimental | Enal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. Receives: Drug: Valsartan 80 mg bid; Drug: Enalapril 10 mg bid; Drug: Sacubitril-Valsartan 200 mg bid; Drug: Icatibant; Drug: Placebo |
| Enal+Pla, S/V+I, Enal+I, S/V+Pla | Experimental | Enal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. Receives: Drug: Valsartan 80 mg bid; Drug: Enalapril 10 mg bid; Drug: Sacubitril-Valsartan 200 mg bid; Drug: Icatibant; Drug: Placebo |
| Enal+Pla, Enal+I, S/V+Pla, S/V+I | Experimental | Enal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. Receives: Drug: Valsartan 80 mg bid; Drug: Enalapril 10 mg bid; Drug: Sacubitril-Valsartan 200 mg bid; Drug: Icatibant; Drug: Placebo |
| Enal+I, S/V+Pla, Enal+Pla, S/V+I | Experimental | Enal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. Receives: Drug: Valsartan 80 mg bid; Drug: Enalapril 10 mg bid; Drug: Sacubitril-Valsartan 200 mg bid; Drug: Icatibant; Drug: Placebo |
| Enal+I, S/V+I, S/V+Pla, Enal+Pla | Experimental | Enal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. Receives: Drug: Valsartan 80 mg bid; Drug: Enalapril 10 mg bid; Drug: Sacubitril-Valsartan 200 mg bid; Drug: Icatibant; Drug: Placebo |
| Enal+I, Enal+Pla, S/V+I, S/V+Pla | Experimental | Enal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. Receives: Drug: Valsartan 80 mg bid; Drug: Enalapril 10 mg bid; Drug: Sacubitril-Valsartan 200 mg bid; Drug: Icatibant; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in systolic blood pressure
Measured: 7-hour period after 7-day intervention
change in plasma cGMP
Measured: 7-hour period after 7-day intervention
Secondary outcomes (11)
heart rate
Measured: 7-hour period after 7-day intervention
renal plasma flow
Measured: 7-hour period after 7-day intervention
glomerular filtration rate
Measured: 7-hour period after 7-day intervention
change in diastolic blood pressure
Measured: 7-hour period after 7-day intervention
fractional excretion of sodium
Measured: 7-hour period after 7-day intervention
urine albumin-to-creatinine ratio
Measured: 7-hour period after 7-day intervention
brain natriuretic peptide (BNP) to N-terminal pro-BNP ratio
Measured: 7-hour period after 7-day intervention
plasminogen activator inhibitor-1
Measured: 7-hour period after 7-day intervention
tissue plasminogen activator
Measured: 7-hour period after 7-day intervention
aldosterone
Measured: 7-hour period after 7-day intervention
urine cGMP
Measured: 7-hour period after 7-day intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2016 (estimated)
- Study startSep 2017 (estimated)
- Primary completionJan 2020 (estimated)
- Study completionJan 2020 (estimated)
Why it stopped: Study is being redesigned and submitted as a new study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure NYHA Class IStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nancy J. Brown, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03005184
- Sponsor's protocol ID
- IRB#161306
- Status last verified
- Jan 2018
- First submitted
- 22 Dec 2016
- Last updated
- 11 Jan 2018
- Results posted
- No
- 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 11 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanism(s) Underlying Cardiovascular Effects of ARB/NEP Inhibition - Aim 2
- ClinicalTrials.gov ID
- NCT03005184
- Acronym / sponsor ID
- IRB#161306
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study is being redesigned and submitted as a new study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- Sep 2017 (estimated)
- Primary completion
- Jan 2020 (estimated)
- Study completion
- Jan 2020 (estimated)
- First posted
- 29 Dec 2016 (estimated)
- 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.
This study tests the hypothesis that endogenous bradykinin contributes to effects of a combined angiotensin receptor blocker/neprilysin inhibitor (LCZ696 or Entresto)
Detailed description
Patients with heart failure (HF) with reduced ejection fraction who qualify for the study will undergo a three-week run-in period in which any prior angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker they were taking will be discontinued and they will be given valsartan 80 mg bid in a single-blind fashion. After the run-in, subjects will undergo four study periods in random order. During two study periods they will receive enalapril 10 mg bid and during two they will receive sacubitril/valsartan (LCZ696) 200 mg bid for seven days. On the seventh day or each period, subjects will complete a study day in which they are randomized to receive either the bradykinin B2 receptor blocker icatibant or placebo intravenously. Each study period will be separated by a three-week washout during which subjects receive valsartan 80 mg bid.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| S/V+Pla, S/V+I, Enal+Pla, Enal+I | Experimental | Drug: Valsartan 80 mg bid, Drug: Enalapril 10 mg bid, Drug: Sacubitril-Valsartan 200 mg bid, Drug: Icatibant, Drug: PlaceboEnal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. |
| S/V+Pla, Enal+I, S/V+I, Enal+Pla | Experimental | Drug: Valsartan 80 mg bid, Drug: Enalapril 10 mg bid, Drug: Sacubitril-Valsartan 200 mg bid, Drug: Icatibant, Drug: PlaceboEnal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. |
| S/V+Pla, Enal+Pla, Enal+I, S/V+I | Experimental | Drug: Valsartan 80 mg bid, Drug: Enalapril 10 mg bid, Drug: Sacubitril-Valsartan 200 mg bid, Drug: Icatibant, Drug: PlaceboEnal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. |
| S/V+I, S/V+Pla, Enal+I, Enal+P | Experimental | Drug: Valsartan 80 mg bid, Drug: Enalapril 10 mg bid, Drug: Sacubitril-Valsartan 200 mg bid, Drug: Icatibant, Drug: PlaceboEnal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. |
| S/V+I, Enal+Pla, S/V+Pla, Enal+I | Experimental | Drug: Valsartan 80 mg bid, Drug: Enalapril 10 mg bid, Drug: Sacubitril-Valsartan 200 mg bid, Drug: Icatibant, Drug: PlaceboEnal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. |
| S/V+I, Enal+I, Enal+Pla, S/V+Pla | Experimental | Drug: Valsartan 80 mg bid, Drug: Enalapril 10 mg bid, Drug: Sacubitril-Valsartan 200 mg bid, Drug: Icatibant, Drug: PlaceboEnal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. |
| Enal+Pla, S/V+Pla, S/V+I, Enal+I | Experimental | Drug: Valsartan 80 mg bid, Drug: Enalapril 10 mg bid, Drug: Sacubitril-Valsartan 200 mg bid, Drug: Icatibant, Drug: PlaceboEnal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. |
| Enal+Pla, S/V+I, Enal+I, S/V+Pla | Experimental | Drug: Valsartan 80 mg bid, Drug: Enalapril 10 mg bid, Drug: Sacubitril-Valsartan 200 mg bid, Drug: Icatibant, Drug: PlaceboEnal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. |
| Enal+Pla, Enal+I, S/V+Pla, S/V+I | Experimental | Drug: Valsartan 80 mg bid, Drug: Enalapril 10 mg bid, Drug: Sacubitril-Valsartan 200 mg bid, Drug: Icatibant, Drug: PlaceboEnal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. |
| Enal+I, S/V+Pla, Enal+Pla, S/V+I | Experimental | Drug: Valsartan 80 mg bid, Drug: Enalapril 10 mg bid, Drug: Sacubitril-Valsartan 200 mg bid, Drug: Icatibant, Drug: PlaceboEnal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. |
| Enal+I, S/V+I, S/V+Pla, Enal+Pla | Experimental | Drug: Valsartan 80 mg bid, Drug: Enalapril 10 mg bid, Drug: Sacubitril-Valsartan 200 mg bid, Drug: Icatibant, Drug: PlaceboEnal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. |
| Enal+I, Enal+Pla, S/V+I, S/V+Pla | Experimental | Drug: Valsartan 80 mg bid, Drug: Enalapril 10 mg bid, Drug: Sacubitril-Valsartan 200 mg bid, Drug: Icatibant, Drug: PlaceboEnal indicated Enalapril 10 mg bid for seven days, and S/V indicates Sacubitril-Valsartan 200 mg bid for seven days. Pla indicates intravenous placebo given on the seventh day of treatment, whereas I indicates intravenous icatibant given on the seventh day of treatment. Each treatment period is separated by a three-week washout during which patients receive Valsartan 80 mg bid. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Stable patients with a reduced EF
- For female subjects, the following conditions must be met:
Key exclusion criteria (33 listed)
- History of hypersensitivity or allergy to any of the study drugs, drugs of similar chemical classes, ACEi, ARBs, or NEPi, as well as known or suspected contraindications to the study drugs
- History of angioedema
- History of pancreatitis or known pancreatic lesions
- History of decompensated HF within the last six months (exacerbation of chronic HF manifested by signs and symptoms that required intravenous therapy or hospitalization)
- History of heart transplant or on a transplant list or with left ventricular assistance device
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 |
|---|---|---|
| Valsartan 80 mg bidoral medication during run-in and washout period | Drug | Enal+I, Enal+Pla, S/V+I, S/V+Pla, Enal+I, S/V+I, S/V+Pla, Enal+Pla, Enal+I, S/V+Pla, Enal+Pla, S/V+I, Enal+Pla, Enal+I, S/V+Pla, S/V+I, Enal+Pla, S/V+I, Enal+I, S/V+Pla, Enal+Pla, S/V+Pla, S/V+I, Enal+I, S/V+I, Enal+I, Enal+Pla, S/V+Pla, S/V+I, Enal+Pla, S/V+Pla, Enal+I, S/V+I, S/V+Pla, Enal+I, Enal+P, S/V+Pla, Enal+I, S/V+I, Enal+Pla, S/V+Pla, Enal+Pla, Enal+I, S/V+I, S/V+Pla, S/V+I, Enal+Pla, Enal+I |
| Enalapril 10 mg bidoral medication | Drug | Enal+I, Enal+Pla, S/V+I, S/V+Pla, Enal+I, S/V+I, S/V+Pla, Enal+Pla, Enal+I, S/V+Pla, Enal+Pla, S/V+I, Enal+Pla, Enal+I, S/V+Pla, S/V+I, Enal+Pla, S/V+I, Enal+I, S/V+Pla, Enal+Pla, S/V+Pla, S/V+I, Enal+I, S/V+I, Enal+I, Enal+Pla, S/V+Pla, S/V+I, Enal+Pla, S/V+Pla, Enal+I, S/V+I, S/V+Pla, Enal+I, Enal+P, S/V+Pla, Enal+I, S/V+I, Enal+Pla, S/V+Pla, Enal+Pla, Enal+I, S/V+I, S/V+Pla, S/V+I, Enal+Pla, Enal+I |
| Sacubitril-Valsartan 200 mg bidoral medication | Drug | Enal+I, Enal+Pla, S/V+I, S/V+Pla, Enal+I, S/V+I, S/V+Pla, Enal+Pla, Enal+I, S/V+Pla, Enal+Pla, S/V+I, Enal+Pla, Enal+I, S/V+Pla, S/V+I, Enal+Pla, S/V+I, Enal+I, S/V+Pla, Enal+Pla, S/V+Pla, S/V+I, Enal+I, S/V+I, Enal+I, Enal+Pla, S/V+Pla, S/V+I, Enal+Pla, S/V+Pla, Enal+I, S/V+I, S/V+Pla, Enal+I, Enal+P, S/V+Pla, Enal+I, S/V+I, Enal+Pla, S/V+Pla, Enal+Pla, Enal+I, S/V+I, S/V+Pla, S/V+I, Enal+Pla, Enal+I |
| Icatibantintravenous medication | Drug | Enal+I, Enal+Pla, S/V+I, S/V+Pla, Enal+I, S/V+I, S/V+Pla, Enal+Pla, Enal+I, S/V+Pla, Enal+Pla, S/V+I, Enal+Pla, Enal+I, S/V+Pla, S/V+I, Enal+Pla, S/V+I, Enal+I, S/V+Pla, Enal+Pla, S/V+Pla, S/V+I, Enal+I, S/V+I, Enal+I, Enal+Pla, S/V+Pla, S/V+I, Enal+Pla, S/V+Pla, Enal+I, S/V+I, S/V+Pla, Enal+I, Enal+P, S/V+Pla, Enal+I, S/V+I, Enal+Pla, S/V+Pla, Enal+Pla, Enal+I, S/V+I, S/V+Pla, S/V+I, Enal+Pla, Enal+I |
| Placebointravenous medication | Drug | Enal+I, Enal+Pla, S/V+I, S/V+Pla, Enal+I, S/V+I, S/V+Pla, Enal+Pla, Enal+I, S/V+Pla, Enal+Pla, S/V+I, Enal+Pla, Enal+I, S/V+Pla, S/V+I, Enal+Pla, S/V+I, Enal+I, S/V+Pla, Enal+Pla, S/V+Pla, S/V+I, Enal+I, S/V+I, Enal+I, Enal+Pla, S/V+Pla, S/V+I, Enal+Pla, S/V+Pla, Enal+I, S/V+I, S/V+Pla, Enal+I, Enal+P, S/V+Pla, Enal+I, S/V+I, Enal+Pla, S/V+Pla, Enal+Pla, Enal+I, S/V+I, S/V+Pla, S/V+I, Enal+Pla, Enal+I |
Primary outcome
change in systolic blood pressure
Time frame: 7-hour period after 7-day intervention
change in plasma cGMP
Time frame: 7-hour period after 7-day intervention
11 secondary outcomes
heart rate
Time frame: 7-hour period after 7-day intervention
renal plasma flow
Time frame: 7-hour period after 7-day intervention
glomerular filtration rate
Time frame: 7-hour period after 7-day intervention
change in diastolic blood pressure
Time frame: 7-hour period after 7-day intervention
fractional excretion of sodium
Time frame: 7-hour period after 7-day intervention
urine albumin-to-creatinine ratio
Time frame: 7-hour period after 7-day intervention
brain natriuretic peptide (BNP) to N-terminal pro-BNP ratio
Time frame: 7-hour period after 7-day intervention
plasminogen activator inhibitor-1
Time frame: 7-hour period after 7-day intervention
tissue plasminogen activator
Time frame: 7-hour period after 7-day intervention
aldosterone
Time frame: 7-hour period after 7-day intervention
urine cGMP
Time frame: 7-hour period after 7-day intervention
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2018.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
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 Valsartan 80 mg bid, Enalapril 10 mg bid and Sacubitril-Valsartan 200 mg bid in people with Heart Failure NYHA Class I and Heart Failure NYHA Class II, run by Vanderbilt University Medical Center 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 33 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: withdrawn, as of the sponsor's last update on 11 Jan 2018. 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?
The study was withdrawn before enrolling participants, so there are no results.
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 systolic blood pressure (time frame: 7-hour period after 7-day intervention). 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 11 Jan 2018.