Tezosentan in the Treatment of Acute Heart Failure

NCT ID: NCT00524433

Last Updated: 2018-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 713 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-04-30
• Study Completion Date: 2005-01-31

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.

Conditions

Acute Heart Failure; Acute Decompensation of Chronic Heart Failure; New Onset of Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

tezosentan

Group Type: EXPERIMENTAL

tezosentan

Intervention Type: DRUG

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

2

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Interventions

tezosentan

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

Intervention Type: DRUG

placebo

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Idorsia Pharmaceuticals Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Oracle Research

Huntsville, Alabama, United States

USC Medical Center

Los Angeles, California, United States

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

University of Miami-Jackson Memorial Hospital

Miami, Florida, United States

University Hospital

Augusta, Georgia, United States

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States

Medical Research Institute

Slidell, Louisiana, United States

Baystate Medical Center-Cardiology Section

Springfield, Massachusetts, United States

Elmhurst Hospital Center

Elmhurst, New York, United States

Columbia Presbyterian Medical Center-Heart Failure Center

New York, New York, United States

New York University School of Medicine

New York, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

LeBauer Cardiovascular Research Foundation

Greensboro, North Carolina, United States

Baylor College of Medicine - Texas Medical Center

Houston, Texas, United States

University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

Alfred Hospital, Monash University, Central and Eastern School

Prahran, Victoria, Australia

Concord Repatriation Hospital

Concord NSW, , Australia

Queen Elizabeth Hospital

Woodville SA, , Australia

Faculty Hospital St. Anna

Brno, , Czechia

Krajska Nemocnice Liberec

Liberec, , Czechia

Klinika Kardiologie IKEM

Prague, , Czechia

University Hospital Vinohrady (FNKV)

Prague, , Czechia

Masaryk Hospital

Ústí nad Labem, , Czechia

Universitatsklinikum der Humboldt-Universitat Berlin, Campus Charite Mitte, Med. Klinik und Poliklinik, Kardiologie

Berlin, , Germany

Universitat Greifswald, Klinik fur Innere Medizin B

Greifswald, , Germany

Asklepios Klinik Langen, Abteilung fur Innere Medizin

Langen, , Germany

Universitatsklinikum Schleswig Holstein, Medizinische Klinik II, Kardiologie

Lübeck, , Germany

Klinik u. Poliklinik F. Inn. Med. II, Univ. Klinik Regensburg

Regensburg, , Germany

Jahn Ferenc, Delpesti Korhaz

Budapest, , Hungary

Polyclinic of the Hospitaler Brothers of St. John of God

Budapest, , Hungary

University of Debrecen

Debrecen, , Hungary

2nd Department of Medicine & Cardiology Centre

Szeged, , Hungary

Cattedra di Cardiologia, c/o Spedali Civili

Brescia, , Italy

Istituto Clinico Humanitas, U.O. Cardiologia Clin. E Insuff. Cardiaca

Rozzano (MI), , Italy

Sentralsykehuset i More og Romsdal, Dept. of Cardiology

Ålesund, , Norway

Aker University Hospital, Div. Cardiology

Oslo, , Norway

Central Hospital in Rogaland, Cardiology Division

Stavanger, , Norway

University Department of Medicine, City Hospital

Birmingham, , United Kingdom

Cardiology Department, Bridlington & District Hospital

Bridlington, , United Kingdom

University of Glasgow West

Glasgow, , United Kingdom

Dept. of Medicine & Therapeutics, University of Leicester

Leicester, , United Kingdom

Countries

United States; Australia; Czechia; Germany; Hungary; Italy; Norway; United Kingdom

References

Cotter G, Davison BA, Milo O, Bourge RC, Cleland JG, Jondeau G, Krum H, O'Connor CM, Metra M, Parker JD, Torre-Amione G, van Veldhuisen DJ, Kobrin I, Rainisio M, Senger S, Edwards C, McMurray JJ, Teerlink JR; VERITAS Investigators. Predictors and Associations With Outcomes of Length of Hospital Stay in Patients With Acute Heart Failure: Results From VERITAS. J Card Fail. 2016 Oct;22(10):815-22. doi: 10.1016/j.cardfail.2015.12.017. Epub 2015 Dec 22.

Reference Type: DERIVED

PMID: 26721775 (View on PubMed)

McMurray JJ, Teerlink JR, Cotter G, Bourge RC, Cleland JG, Jondeau G, Krum H, Metra M, O'Connor CM, Parker JD, Torre-Amione G, van Veldhuisen DJ, Lewsey J, Frey A, Rainisio M, Kobrin I; VERITAS Investigators. Effects of tezosentan on symptoms and clinical outcomes in patients with acute heart failure: the VERITAS randomized controlled trials. JAMA. 2007 Nov 7;298(17):2009-19. doi: 10.1001/jama.298.17.2009.

Reference Type: DERIVED

PMID: 17986694 (View on PubMed)

Other Identifiers

AC-051-307

Identifier Type: -

Identifier Source: org_study_id