Tezosentan in the Treatment of Acute Heart Failure

Phase 3

Completed

Conditions: Acute Heart Failure
Acute Decompensation of Chronic Heart Failure
New Onset of Heart Failure

Interventions: Drug: placebo
Drug: tezosentan

Registration Number: NCT00524433

Lead Sponsor: Idorsia Pharmaceuticals Ltd.

Brief Summary: The randomized patients with acute heart failure will be stratified based on the presence or absence of a Swan-Ganz catheter and assigned to receive either tezosentan 5 mg/h for the first 30 minutes and 1 mg/h thereafter or matching placebo in a 1:1 manner. The duration of the treatment is 24 hours up to 72 hours. The duration of the follow-up period is 30 days after treatment initiation for death, re-hospitalizations and SAEs followed by a follow-up period of 5 months for vital status.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 713

Inclusion Criteria

1.Patients 18 years of age or older. 2.Male or non-breast-feeding, non-pregnant female (only females who are post menopausal, surgically sterile or practicing a reliable method of contraception).

3.Acute heart failure (ischemic or non-ischemic). 4.Randomization within 24 hours of hospitalization (including emergency room stay) for acute heart failure.

5.Dyspnea at rest as assessed by the patient and breathing rate ³ 24/min (measured during 60 seconds).

6.At least two out of the following four criteria: · elevated BNP or N terminal pro-BNP (more than three times the upper limit of normal for the site) in patients not treated with nesiritide,· clinical evidence of pulmonary congestion/edema (e.g., rales or crackles more than a third above bases),· evidence of pulmonary congestion on chest X-ray, · left ventricular systolic dysfunction (EF < 40% or wall motion index £ 1.2 within 12 months prior to randomization).

7.Patients in need of i.v. therapy for acute heart failure and who have received at least one dose of i.v. diuretic within 24 hours prior to study drug initiation (last bolus dose must have been more than 2 hours prior to study drug initiation).

8.Written informed consent.

Exclusion Criteria

Criteria only for patients hemodynamically monitored:
1. Baseline cardiac index > 2.5 l/min/m2 and/or PCWP < 20 mmHg within 6 hours prior to study drug initiation.
  
  Criteria for all patients:
2. Patients not receiving i.v. vasodilators (e.g., nitrates, nitroprusside, nesiritide) at baseline: supine systolic blood pressure < 100 mmHg. Patients receiving i.v. vasodilators (e.g., nitrates, nitroprusside, nesiritide) at baseline: supine systolic blood pressure < 120 mmHg.
3. Cardiogenic shock within the last 48 hours or evidence of volume depletion.
4. Ongoing myocardial ischaemia, coronary revascularisation procedure (PCI or CABG) during current admission or planned revascularisation.
5. ST-segment elevation myocardial infarction or administration of thrombolytic therapy.
6. Baseline creatinine ≥ 2.5 mg/dl (221 mmol/l).
7. Baseline hemoglobin < 10 g/dl or a hematocrit < 30%.
8. Hemodialysis, ultrafiltration or peritoneal dialysis within the last 7 days.
9. Heart failure due to active myocarditis, obstructive hypertrophic cardiomyopathy, congenital heart disease, restrictive cardiomyopathy or constrictive pericarditis. Heart failure caused by valvular disease.
10. Acute heart failure associated with uncontrolled hemodynamically relevant atrial fibrillation/flutter or ventricular rhythm disturbances.
11. Acute heart failure secondary to clinical evidence of digoxin toxicity or any other drug-related toxicity.
12. Significant chronic and/or acute lung disease that might interfere with the ability to interpret the dyspnea assessments or hemodynamic measurements (e.g., severe chronic obstructive pulmonary disease or acute pneumonia).
13. Mechanical circulatory or ventilatory support. Prior CPAP use is allowed, if discontinued at least 2 hours prior to study drug initiation.
14. Acute systemic infection/sepsis or other illness with a life expectancy less than 30 days.
15. Coronary artery bypass graft, or other cardiac surgery, or major non-cardiac surgery within the last 30 days.
16. Patients who received another investigational drug within 30 days prior to randomization.
17. Re-randomization in the current study.
18. Any factors that might interfere with the study conduct or interpretation of the results such as known drug or alcohol dependence.
19. Concomitant treatment with cyclosporin A or tacrolimus.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	placebo	-
1	tezosentan	tezosentan

Primary Outcome Measures

Name	Time	Method
Incidence of death or worsening heart failure	within 7 days following study drug initiation

Secondary Outcome Measures

Name	Time	Method
Patient's dyspnea assessment, measured using a visual analog scale	Over first 24 hours

Trial Locations

Locations (42): Oracle Research
🇺🇸
Huntsville, Alabama, United States
USC Medical Center
🇺🇸
Los Angeles, California, United States
Jacksonville Center for Clinical Research
🇺🇸
Jacksonville, Florida, United States
University Hospital
🇺🇸
Augusta, Georgia, United States
University of Iowa Hospital and Clinics
🇺🇸
Iowa City, Iowa, United States
University of Miami-Jackson Memorial Hospital
🇺🇸
Miami, Florida, United States
Columbia Presbyterian Medical Center-Heart Failure Center
🇺🇸
New York, New York, United States
Elmhurst Hospital Center
🇺🇸
Elmhurst, New York, United States
Baystate Medical Center-Cardiology Section
🇺🇸
Springfield, Massachusetts, United States
New York University School of Medicine
🇺🇸
New York, New York, United States
LeBauer Cardiovascular Research Foundation
🇺🇸
Greensboro, North Carolina, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
University of Texas, MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Klinika Kardiologie IKEM
🇨🇿
Prague, Czechia
Baylor College of Medicine - Texas Medical Center
🇺🇸
Houston, Texas, United States
Concord Repatriation Hospital
🇦🇺
Concord NSW, Australia
Queen Elizabeth Hospital
🇦🇺
Woodville SA, Australia
Faculty Hospital St. Anna
🇨🇿
Brno, Czechia
Krajska Nemocnice Liberec
🇨🇿
Liberec, Czechia
Asklepios Klinik Langen, Abteilung fur Innere Medizin
🇩🇪
Langen, Germany
University Hospital Vinohrady (FNKV)
🇨🇿
Prague, Czechia
Universitat Greifswald, Klinik fur Innere Medizin B
🇩🇪
Greifswald, Germany
Universitatsklinikum der Humboldt-Universitat Berlin, Campus Charite Mitte, Med. Klinik und Poliklinik, Kardiologie
🇩🇪
Berlin, Germany
Universitatsklinikum Schleswig Holstein, Medizinische Klinik II, Kardiologie
🇩🇪
Lubeck, Germany
Klinik u. Poliklinik F. Inn. Med. II, Univ. Klinik Regensburg
🇩🇪
Regensburg, Germany
University Department of Medicine, City Hospital
🇬🇧
Birmingham, United Kingdom
University of Glasgow West
🇬🇧
Glasgow, United Kingdom
Sentralsykehuset i More og Romsdal, Dept. of Cardiology
🇳🇴
Alesund, Norway
Central Hospital in Rogaland, Cardiology Division
🇳🇴
Stavanger, Norway
Cardiology Department, Bridlington & District Hospital
🇬🇧
Bridlington, United Kingdom
Dept. of Medicine & Therapeutics, University of Leicester
🇬🇧
Leicester, United Kingdom
Cattedra di Cardiologia, c/o Spedali Civili
🇮🇹
Brescia, Italy
Istituto Clinico Humanitas, U.O. Cardiologia Clin. E Insuff. Cardiaca
🇮🇹
Rozzano (MI), Italy
Masaryk Hospital
🇨🇿
Usti nad Labem, Czechia
2nd Department of Medicine & Cardiology Centre
🇭🇺
Szeged, Hungary
Medical Research Institute
🇺🇸
Slidell, Louisiana, United States
Aker University Hospital, Div. Cardiology
🇳🇴
Oslo, Norway
Polyclinic of the Hospitaler Brothers of St. John of God
🇭🇺
Budapest, Hungary
Alfred Hospital, Monash University, Central and Eastern School
🇦🇺
Prahran, Victoria, Australia
University of Debrecen
🇭🇺
Debrecen, Hungary
Jahn Ferenc, Delpesti Korhaz
🇭🇺
Budapest, Hungary
University of North Carolina
🇺🇸
Chapel Hill, North Carolina, United States

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Tezosentan in the Treatment of Acute Heart Failure

Recruitment & Eligibility

Study & Design

Trial Locations

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