Clinical trial NCT00283361: ZP120 Add-on to Furosemide in Treatment of Acute or Sub-Acute Decompensated Heart Failure
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Heart Failure, Congestive
Lead sponsor: Zealand Pharma
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2006-01-27
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Change in dyspnea severity
Secondary outcomes:
measure: Change in 6-minute walk test performance
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: LAC-USC Medical Center-Division of Cardiology
state: California
city: Los Angeles
country: United States
facility: VA Medical Center -WLA
state: California
city: San Diego
country: United States
facility: UCSD Medical Center
state: California
city: San Francisco
country: United States
facility: San Francisco VA Medical Center
state: California
city: Denver
country: United States
facility: University of CO Health Sciences Center
state: Colorado
city: Melbourne
country: United States
facility: Health First Clinical Research Institute
state: Florida
city: Miami
country: United States
facility: Univ. of Miami Miller School of Medicine, Jackson Memorial Medical Center
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital/The Emory Clinic
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Anderson
country: United States
facility: Community Hospital Anderson/Community Clinical Research Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Heart Failure Treatment Program
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Missoula
country: United States
facility: The International Heart Institute
state: Montana
city: Lincoln
country: United States
facility: Bryan LGH Heart Institute
state: Nebraska
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Lancaster
country: United States
facility: Lancaster Heart Foundation
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: San Antonio
country: United States
facility: Alamo Clinical Research Associates
state: Texas
Study officials:
References: