Tezosentan in Acute Heart Failure

Phase 3

Completed

• Conditions: Acute Heart Failure; Acute Decompensation of Chronic Heart Failure; New Onset of Heart Failure
• Interventions: Drug: tezosentan

• Registration Number: NCT00525707
• 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

Study Timeline

• Study Start: 2003-04
• Primary Completion: 2005-01
• Study Completion: 2005-01
• Study First Submitted: 2007-08-31
• Study First Submitted QC: 2007-09-05
• Study First Posted: 2007-09-06
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-06
• Last Update Posted: 2018-07-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 735

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
1	tezosentan	tezosentan delivered i.v. at 20 mL/h (5 mg/h) for 30 min followed by 4ML/h (1 mg/h) for 23.5 to 71.5 h (24 to 72 h in total)
2	tezosentan	-

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (35)

Cardio Centro Ticino, Servizio Cardiovasculare; 🇨🇭 Lugano, Switzerland

Kategra I Klinika Kardiolgii AM; 🇵🇱 Wroclaw, Poland

Denver VAMC; 🇺🇸 Denver, Colorado, United States

The Heart Hospital at Alledgheny General, Division of Cardiology; 🇺🇸 Pittsburgh, Pennsylvania, United States

Veterans Affairs Medical Center; 🇺🇸 Houston, Texas, United States

University of Alabama-Birmingham; 🇺🇸 Birmingham, Alabama, United States

Advanced Heart Failure and Transplant Service, Palo Alto VA Health Care System, Cardiology Section; 🇺🇸 Palo Alto, California, United States

Tyler Cardiovascular Consultants; 🇺🇸 Tyler, Texas, United States

AKH University of Vienna, Abt. Medizinische Kardiologie; 🇦🇹 Vienna, Austria

Roskilde Amt Sygehus; 🇩🇰 Roskilde, Denmark

Hopital Ambroise Pare, Service de Cardiologie; 🇫🇷 Boulogne, France

Danville Medical Center; 🇺🇸 Danville, Virginia, United States

Heart Failure clinic C.H. Dubos; 🇫🇷 Pontoise, France

Medizinische Klinik I, Universitatsklinikum Aachen; 🇩🇪 Aachen, Germany

I Klinika Kardiolgii, Collegium Medicum UJ; 🇵🇱 Krakow, Poland

Medical Associates, Bellebue; 🇺🇸 Bellevue, Washington, United States

Hopitaux Universitaires de Strasbourg, Hopital Hautepierre; 🇫🇷 Strasbourg, France

Nazareth Hospital EMMS; 🇮🇱 Nazareth, Israel

CHU Rangueil, Cardiologie A; 🇫🇷 Toulouse, France

Campus Virchow-Klinikum, Medizinishe Klinik mit Schwerpunkt Kardiologie; 🇩🇪 Berlin, Germany

Dept. of Cardiology, University of Athens, Alexandra Hospital; 🇬🇷 Athens, Greece

Georg-August-Universitat Gottingen, Zentrum fur Innere Med; 🇩🇪 Gottingen, Germany

Barzilai Hospital; 🇮🇱 Ashkelon, Israel

Carmel Medical Center; 🇮🇱 Haifa, Israel

Klinika Chorob Serca, Akademia Medyczna w Gdansku; 🇵🇱 Gdansk, Poland

Klinika Kardiologii i Chorob Wewnetrznych, Samodzielny Publiczny Szpital; 🇵🇱 Bydgoszcz, Poland

Hadassah Hospital; 🇮🇱 Jerusalem, Israel

Wolfson Medical Center; 🇮🇱 Holon, Israel

Assaf-Harofeh Medical Center; 🇮🇱 Zerifin, Israel

Centre Hospitalier Universitaire Vaudois (CHUV); 🇨🇭 Lausanne, Switzerland

University Hospital Zurich; 🇨🇭 Zurich, Switzerland

Institute of Cardiology College, College of Medicine of Jagellonian University; 🇵🇱 Krakow, Poland

Glasgow Royal Infirmary; 🇬🇧 Glasgow, United Kingdom

Hull Royal Infirmary; 🇬🇧 Kingston Upon Hull, United Kingdom

Scunthorpe General Hospital; 🇬🇧 Scunthorpe, United Kingdom