Effects of MK7418 on Diuresis and Renal Function in Congestive Heart Failure Patients

A Randomized, Double-Blind, Placebo Controlled Dose-Ranging Study of The Effects of MK7418, Both as Monotherapy and in Combination With Furosemide, On Diuresis and Renal Function in Patients With Congestive Heart Failure (CHF) And Renal Impairment Treated With Oral Loop Diuretics Who Require Hospitalization For Fluid Overload

A study to determine the most appropriate dose of MK7418 in heart failure patients presenting with symptoms of volume overload requiring increased diuretic doses.

Study Overview

• Status: Completed
• Conditions: Renal Impairment; Congestive Heart Failure
• Intervention / Treatment: Drug: rolofyline; Drug: Comparator Placebo (unspecified)

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Be able to provide written informed consent,
• Be a male or female at least 18 years of age,
• Be hospitalized for fluid overload requiring IV diuretic therapy
• History of use of diuretic therapy for CHF (including this admission),
• Be admitted to the hospital within 36 hours of the mandatory dose of IV furosemide 40 mg at between 2000 and 2200 hour on Day -1

Exclusion Criteria:

• Have had a myocardial infarction within 30 days prior to Day -1
• Be pregnant or breast-feeding
• Have received intravascular contrast material within the preceding 14 days; or have acute contrast nephropathy
• Have had implantation of an automated implanted cardiac defibrillator (AICD) or synchronization device within the preceding 7 days
• Currently require mechanical ventilation, ultrafiltration, or hemodialysis,
• Have symptomatic ventricular tachycardia
• Be admitted for heart transplant surgery or have had a heart transplant,
• Have any other concomitant life-threatening disease,
• Have participated in a clinical trial of an investigational drug or device within 30 days before randomization
• Have a positive urine pregnancy test (for women of child-bearing capacity)
• Have an allergy to soybean oil and/or eggs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; rolofyline 2.5 mg IV QD	Drug: rolofyline; rolofyline 2.5 mg IV QD; 15 mg IV QD; 30 mg IV QD; 60 mg IV QD; 3 days; Other Names: MK7418
Experimental: 2; rolofyline 15 mg IV QD	Drug: rolofyline; rolofyline 2.5 mg IV QD; 15 mg IV QD; 30 mg IV QD; 60 mg IV QD; 3 days; Other Names: MK7418
Experimental: 3; rolofyline 30 mg IV QD	Drug: rolofyline; rolofyline 2.5 mg IV QD; 15 mg IV QD; 30 mg IV QD; 60 mg IV QD; 3 days; Other Names: MK7418
Experimental: 4; rolofyline 60 mg IV QD	Drug: rolofyline; rolofyline 2.5 mg IV QD; 15 mg IV QD; 30 mg IV QD; 60 mg IV QD; 3 days; Other Names: MK7418
Placebo Comparator: 5; placebo for rolofyline IV QD	Drug: Comparator Placebo (unspecified); Matching placebo for rolofyline IV QD; 3 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To measure the diuretic effect of a single dose of the study medication (monotherapy) over six hours compared to a single dose of IV placebo (monotherapy) in CHF patients with renal impairment	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the optimal dose range of intravenous (IV) study medication combination with IV furosemide, with or without other diuretics, in preventing deterioration of renal function in CHF patients	30 Days

Collaborators and Investigators

• Sponsor: NovaCardia, Inc.
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): August 1, 2005

Study Registration Dates

• First Submitted: April 1, 2008
• First Submitted That Met QC Criteria: April 1, 2008
• First Posted (Estimate): April 4, 2008

Study Record Updates

• Last Update Posted (Estimate): April 4, 2008
• Last Update Submitted That Met QC Criteria: April 1, 2008
• Last Verified: April 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Heart Failure; Renal Insufficiency; Physiological Effects of Drugs; Natriuretic Agents; Diuretics; Rolofylline
• Other Study ID Numbers: 2007_806; MK7418-201