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

Merck Sharp & Dohme (MSD)

Status and phase: Withdrawn; Phase 1

Conditions: Heart Failure

Treatments: Procedure: Loop Diuretic Withdrawal/Salt Load; Procedure: Blood Draw

Study type: Interventional

Funder types: Industry

Identifiers

NCT02364752

0000-344

Details and patient eligibility

About

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.

Sex: All

Ages: 40 to 80 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 3 patient groups

Healthy

Experimental group

Description:

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.

Treatment:

Procedure: Blood Draw

Mild/moderate heart failure (HF)

Experimental group

Description:

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.

Treatment:

Procedure: Loop Diuretic Withdrawal/Salt Load

Procedure: Blood Draw

Severe HF

Experimental group

Description:

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.

Treatment:

Procedure: Loop Diuretic Withdrawal/Salt Load

Procedure: Blood Draw