ZP120 Add-on to Furosemide in Treatment of Acute or Sub-Acute Decompensated Heart Failure

Condition(s) targeted: Heart Failure, Congestive

Intervention: ZP120 (Drug); I.v. catherization (Procedure); 6-minutes walk performance (Procedure); Dyspnea severity assessment (Behavioral); Blood sampling for laboratory tests (Procedure); ECG (Procedure); Physical examination (Procedure)

Phase: Phase 2

Status: Terminated

Sponsored by: Zealand Pharma

The main purpose of this study is to see if the experimental drug ZP120, when given with the approved drug furosemide to patients with acute or sub-acute heart failure, can reduce the amount of fluid in the patients' lungs and make breathing easier.

Official title: A Phase II,Randomized, Double-Blind, Flexible Dose Study of ZP120 I.V. Infusion as Add-On Therapy in Patients With Acute or Sub-Acute Decompensated Chronic Heart Failure NYHA Class III-IV Treated With Furosemide

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Change in dyspnea severity

Secondary outcome: Change in 6-minute walk test performance

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Male or female patients, age 18 years or more

2. A diagnosis of acute or subacute decompensated chronic heart failure, either ischemic or nonischemic, requiring hospitalization, and currently treated with furosemide, torsemide, or bumetadine, and other evidence based optimal treatment for heart failure. Patients must have the clinical diagnosis of CHF made at least 3 month prior to enrollment

3. Ambulatory

4. Objective signs of LVD corresponding to a LVEF < 45%, documented by any accepted method within the previous 12 months. If documentation is not available within the required time frame, LVEF must be assessed prior to enrollment

5. a) Worsening heart failure symptoms (current NYHA class III-IV). Patients must experience worsening of at least one of the symptoms described below at the time of entry into the study:

Dyspnea Symptoms:

- Dyspnea (labored or difficult breathing) at rest

- Worsening dyspnea (labored or difficult breathing) on minimal exertion

- Worsening orthopnea (difficult breathing except in the upright position)

- Increased frequency of nocturnal dyspnea (awaken from sleep due to respiratory

distress)

b) Clinical evidence of volume overload such as weight gain over previous few days, peripheral edema, hepatic congestion with ascites, pulmonary congestion, or pleural effusion

6. Females of childbearing potential must have a negative pregnancy test at enrollment. A female is considered to be of childbearing potential unless she is post-menopausal (no menses for at least 12 consecutive months) or without a uterus and/or both ovaries

7. Ability to understand and willing to sign Informed Consent Form

Exclusion Criteria:

1. Incapable of taking the 6-minute walk test due to any condition unrelated to heart failure, e. g., muscular or skeletal disability

2. Valvular heart disease requiring surgical intervention (during the course of the study. Patients with heart failure due to or associated with uncorrected primary valvular disease, malfunctioning artificial heart valve, or uncorrected congenital heart disease)

3. History of or clinically significant evidence of any severe disease other than heart failure that preclude participation and complicate the evaluation of study results from the local laboratory:

- Hepatic disease (AST, ALT, total bilirubin > 3 times Upper Limit of Normal (ULN),

renal disease (S-Creatinine > 2. 5 mg/dL),

- Uncontrolled insulin-dependent diabetes mellitus with a history of frequent

hypoglycemic episodes or frequent hospitalizations for hyperglycemia,

- Cancer (excluding treated non-melanoma skin cancer)

4. Unstable angina, cardiogenic shock, or acute pulmonary edema requiring any of the following: Nitroprusside, intravenous nitroglycerin, nesiritide, intravenous inotrope, or need for endotracheal intubation and mechanical ventilation

5. Acute myocardial infarction and/or myocardial infarction within 30 days (prior to enrollment) as diagnosed by investigator’s evaluation of clinical symptoms, ECG, and/or biochemical markers of cardiac injury

6. Cardiac arrest (patients with history of cardiac arrest within 12 months unless precipitated by an event such as an acute myocardial infarction, induction by catheter placement, severe transient electrolyte abnormality, by an electrophysiology procedure, or addressed by Automatic Implantable Cardioverter Defibrillator placement. Patients with increased risk of cardiac arrest, QTc > 450 msec, atrial ventricular block II or III, etc.)

7. Sustainable VT/VF within 30 days (> 15 seconds long; patients with enrollment ECG showing ventricular tachycardia or premature ventricular complexes associated with symptoms, or ventricular tachycardia of 6 beats)

8. Uncontrolled atrial fibrillation on enrollment ECG with a ventricular rate >120 bpm

9. Cardiac surgery within the last month or acutely required PCI (patients who have undergone a cardiac revascularization, valvular surgery, or biventricular resynchronization procedure within 30 days. Patients who have had ventricular reduction surgery or cardiac myoplasty and patients with mechanical ventricular assist device)

10. Systolic blood pressure < 90 mmHg and > 200 mmHg

11. Pulmonary embolism or DVT or history of pulmonary embolism or DVT within 6 months prior to enrollment

12. Severe obstructive or restrictive pulmonary disease, patients with primary pulmonary hypertension and heart failure secondary to pulmonary disease, and severe pulmonary infection

13. I. v. vasoactive treatment, e. g. vasodilators, positive inotropic agents, within 24 hours prior to enrollment (see details in Appendix E)

14. Participation in another study evaluating an experimental treatment within the last 30 days which potentially could bias the outcome of this study

15. Previous treatment with ZP120

16. Patients known to abuse or actively abusing alcohol or illicit drugs. Abuse of alcohol is defined as the usual daily intake of more than 100 grams of ethanol per day, or more than approximately six 12-ounce bottles of beer, one 750 mL bottle of wine, or 250 mL of 80 proof spirits

17. Inability or unwillingness to provide informed consent

18. BMI outside range of 20-50 kg/m2 (BMI equal to 20 and 50 kg/m2 is accepted)

19. Any other condition or therapy, which in the opinion of the Principal Investigator would make the patient unsuitable for this study

VA Medical Center -WLA, Los Angeles, California 90073, United States

San Francisco VA Medical Center, San Francisco, California 94121, United States

LAC-USC Medical Center-Division of Cardiology, Los Angeles, California 90073, United States

UCSD Medical Center, San Diego, California 92103-8411, United States

University of CO Health Sciences Center, Denver, Colorado 123456, United States

Univ. of Miami Miller School of Medicine, Jackson Memorial Medical Center, Miami, Florida 33136, United States

Health First Clinical Research Institute, Melbourne, Florida 32901, United States

Northside Hospital, Atlanta, Georgia 30342, United States

Emory University Hospital/The Emory Clinic, Atlanta, Georgia 30322, United States

Rush University Medical Center, Chicago, Illinois 60612, United States

Community Hospital Anderson/Community Clinical Research Center, Anderson, Indiana 46011, United States

University of Iowa Heart Failure Treatment Program, Iowa City, Iowa 52242, United States

University of Maryland, Baltimore, Maryland 21201, United States

Henry Ford Hospital, Detroit, Michigan 48202, United States

Hennepin County Medical Center, Minneapolis, Minnesota 55415, United States

The International Heart Institute, Missoula, Montana 59802, United States

Bryan LGH Heart Institute, Lincoln, Nebraska 68510, United States

University of Rochester Medical Center, Rochester, New York 14618, United States

Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States

Lancaster Heart Foundation, Lancaster, Pennsylvania 17603, United States

Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141, United States

Alamo Clinical Research Associates, San Antonio, Texas 78212, United States

Starting date: January 2006
Ending date: December 2006
Last updated: February 27, 2007