A Study Evaluating Biomarkers in Participants With Heart Failure (MK-0000-344)

Phase 1

Withdrawn

• Conditions: Heart Failure
• Interventions: Procedure: Blood Draw; Procedure: Loop Diuretic Withdrawal/Salt Load

• Registration Number: NCT02364752
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The aim of this 2-part study is to assess B-type natriuretic peptide (BNP) as well as other circulating and imaging biomarkers in myocardial function. Part 1 assesses biomarker levels in healthy participants and participants with cardiac dysfunction. Part 2 assesses BNP and other circulating biomarker levels, and performs imaging in participants with cardiac dysfunction who continued from Part 1. The primary hypothesis is that compared to healthy participants, biomarker levels are elevated in participants with mild/moderate and severe cardiac dysfunction.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-02-10
• Study First Submitted QC: 2015-02-10
• Study First Posted: 2015-02-18
• Study Start: 2015-09
• Status Verified: 2016-03
• Primary Completion: 2016-03
• Last Update Submitted: 2016-03-10
• Last Update Posted: 2016-03-11
• Study Completion: 2016-11

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• female of reproductive potential must demonstrate non-pregnant state, and agree to use two acceptable methods of birth control
• postmenopausal or surgically sterile female
• have a Body Mass Index (BMI) >= 18 and =< 35 kg/m^2, inclusive
• healthy participants are in general good health
• participants with HF have no untreated, significant health issue from other co-morbidities, e.g. uncontrolled hypertension
• is willing to undergo echocardiography, CMR, and other study assessments
• participants with HF have a diagnosis of cardiomyopathy, and slight to moderate limitation of physical activity, but are comfortable at rest
• participants with HF are on a stable medical therapy for HF for two weeks prior to start of Part 1
• participants with HF are on a stable diuretic regimen of >= 40 mg/day furosemide or >= 10 mg/day torsemide for at least 2 weeks prior to start of Part 1

Exclusion Criteria

• has any clinically significant, uncontrolled renal, endocrine (except Type II Diabetes), neurological, hepatic, immunological or inflammatory disease
• has a history of cancer (malignancy)
• had major surgery or donated/lost approximately 500 mL of blood within 4 weeks prior to screening
• participated in another investigational trial within 4 weeks prior to screening
• excepting permitted medications, uses prescription, or non-prescription drugs or herbal remedies 2 weeks prior to enrollment until completion of trial
• takes medications that affect BNP levels within 30 days prior to screening
• undergoes high-intensity physical exercise from 1 week prior to pretrial visit until completion of trial
• has implanted or embedded metal objects in body that in response to a magnetic field could cause injury
• suffers from claustrophobia making them unable to undergo CMR scanning
• consumes alcohol for 7 days prior to screening until completion of study
• consumes excessive amounts of caffeinated beverages
• uses cannabis regularly, or any illicit drugs, or has a history of drug (including alcohol) abuse within prior 12 months

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Severe HF	Loop Diuretic Withdrawal/Salt Load	Part 1: Blood is obtained from participants with severe HF on 3 consecutive days, and participants undergo CMR and 2DSTE on one of those 3 days. Part 2: Within 5 days of completing Part 1 participants have a 24 hour loop diuretic withdrawal, and 15 hour 0.9% normal saline infusion; followed by a blood draw, CMR and 2DSTE.
Healthy	Blood Draw	Part 1: Blood is obtained from healthy participants on 3 consecutive days, and participants undergo Cardiac Magnetic Resonance Imaging (CMR) and two-dimensional speckle tracking echocardiography (2DSTE) on one of those 3 days.
Mild/moderate heart failure (HF)	Blood Draw	Part 1: Blood is obtained from participants with mild/moderate HF on 3 consecutive days, and participants undergo CMR and 2DSTE on one of those 3 days. Part 2: Within 5 days of completing Part 1 participants have a 24 hour loop diuretic withdrawal, and 15 hour 0.9% normal saline infusion; followed by a blood draw, CMR and 2DSTE.
Mild/moderate heart failure (HF)	Loop Diuretic Withdrawal/Salt Load	Part 1: Blood is obtained from participants with mild/moderate HF on 3 consecutive days, and participants undergo CMR and 2DSTE on one of those 3 days. Part 2: Within 5 days of completing Part 1 participants have a 24 hour loop diuretic withdrawal, and 15 hour 0.9% normal saline infusion; followed by a blood draw, CMR and 2DSTE.
Severe HF	Blood Draw	Part 1: Blood is obtained from participants with severe HF on 3 consecutive days, and participants undergo CMR and 2DSTE on one of those 3 days. Part 2: Within 5 days of completing Part 1 participants have a 24 hour loop diuretic withdrawal, and 15 hour 0.9% normal saline infusion; followed by a blood draw, CMR and 2DSTE.

Primary Outcome Measures

Name	Time	Method
Level of total BNP in Part 1	Up to Day 3
Level of total BNP in Part 2	Up to Day 1 post-loop diuretic withdrawal (Up to Day 10)

Secondary Outcome Measures

Name	Time	Method
Level of active BNP in Part 1	Up to Day 3
Level of active BNP in Part 2	Up to Day 1 post-loop diuretic withdrawal (Up to Day 10)
Ratio of total BNP/active BNP in Part 1	Up to Day 3
Ratio of total BNP/active BNP in Part 2	Up to Day 1 post-loop diuretic withdrawal (Up to Day 10)