Tezosentan in the Treatment of Acute Heart Failure

NCT00524433 | Completed Phase 3

• 1 other identifier: AC-051-307
• Study Type: interventional
• Target: 713
• Locations: 8 countries
• Sites: 42

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

Keywords

acute heart failure; acute decompensation of chronic heart failure; new onset of heart failure; tezosentan; Actelion

Outcome Measures

Primary Outcomes (1)

• Incidence of death or worsening heart failure

  within 7 days following study drug initiation

Secondary Outcomes (1)

• Patient's dyspnea assessment, measured using a visual analog scale

  Over first 24 hours

Study Arms (2)

1

EXPERIMENTAL

tezosentan

Drug: tezosentan

2

PLACEBO COMPARATOR

Drug: placebo

Interventions

tezosentan 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)

1

placebo DRUG

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Acute heart failure (ischemic or non-ischemic). 4.Randomization within 24 hours of hospitalization (including emergency room stay) for acute heart failure.
• Dyspnea at rest as assessed by the patient and breathing rate ³ 24/min (measured during 60 seconds).
• 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).
• 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).
• Written informed consent.

You may not qualify if:

• Criteria only for patients hemodynamically monitored:
• 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:
• 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.
• Cardiogenic shock within the last 48 hours or evidence of volume depletion.
• Ongoing myocardial ischaemia, coronary revascularisation procedure (PCI or CABG) during current admission or planned revascularisation.
• ST-segment elevation myocardial infarction or administration of thrombolytic therapy.
• Baseline creatinine ≥ 2.5 mg/dl (221 mmol/l).
• Baseline hemoglobin \< 10 g/dl or a hematocrit \< 30%.
• Hemodialysis, ultrafiltration or peritoneal dialysis within the last 7 days.
• Heart failure due to active myocarditis, obstructive hypertrophic cardiomyopathy, congenital heart disease, restrictive cardiomyopathy or constrictive pericarditis. Heart failure caused by valvular disease.
• Acute heart failure associated with uncontrolled hemodynamically relevant atrial fibrillation/flutter or ventricular rhythm disturbances.
• Acute heart failure secondary to clinical evidence of digoxin toxicity or any other drug-related toxicity.
• 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).
• Mechanical circulatory or ventilatory support. Prior CPAP use is allowed, if discontinued at least 2 hours prior to study drug initiation.

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (42)

Oracle Research

Huntsville, Alabama, United States

Location

USC Medical Center

Los Angeles, California, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Location

University of Miami-Jackson Memorial Hospital

Miami, Florida, United States

Location

University Hospital

Augusta, Georgia, United States

Location

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States

Location

Medical Research Institute

Slidell, Louisiana, United States

Location

Baystate Medical Center-Cardiology Section

Springfield, Massachusetts, United States

Location

Elmhurst Hospital Center

Elmhurst, New York, United States

Location

Columbia Presbyterian Medical Center-Heart Failure Center

New York, New York, United States

Location

New York University School of Medicine

New York, New York, United States

Location

University of North Carolina

Chapel Hill, North Carolina, United States

Location

Duke University Medical Center

Durham, North Carolina, United States

Location

LeBauer Cardiovascular Research Foundation

Greensboro, North Carolina, United States

Location

Baylor College of Medicine - Texas Medical Center

Houston, Texas, United States

Location

University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

Location

Alfred Hospital, Monash University, Central and Eastern School

Prahran, Victoria, Australia

Location

Concord Repatriation Hospital

Concord NSW, Australia

Location

Queen Elizabeth Hospital

Woodville SA, Australia

Location

Faculty Hospital St. Anna

Brno, Czechia

Location

Krajska Nemocnice Liberec

Liberec, Husova 10, Czechia

Location

Klinika Kardiologie IKEM

Prague, Czechia

Location

University Hospital Vinohrady (FNKV)

Prague, Czechia

Location

Masaryk Hospital

Ústí nad Labem, Czechia

Location

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

Berlin, Germany

Location

Universitat Greifswald, Klinik fur Innere Medizin B

Greifswald, Germany

Location

Asklepios Klinik Langen, Abteilung fur Innere Medizin

Langen, Germany

Location

Universitatsklinikum Schleswig Holstein, Medizinische Klinik II, Kardiologie

Lübeck, Germany

Location

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

Regensburg, Germany

Location

Jahn Ferenc, Delpesti Korhaz

Budapest, Hungary

Location

Polyclinic of the Hospitaler Brothers of St. John of God

Budapest, Hungary

Location

University of Debrecen

Debrecen, Hungary

Location

2nd Department of Medicine & Cardiology Centre

Szeged, Hungary

Location

Cattedra di Cardiologia, c/o Spedali Civili

Brescia, Italy

Location

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

Rozzano (MI), Italy

Location

Sentralsykehuset i More og Romsdal, Dept. of Cardiology

Ålesund, Norway

Location

Aker University Hospital, Div. Cardiology

Oslo, Norway

Location

Central Hospital in Rogaland, Cardiology Division

Stavanger, Norway

Location

University Department of Medicine, City Hospital

Birmingham, United Kingdom

Location

Cardiology Department, Bridlington & District Hospital

Bridlington, United Kingdom

Location

University of Glasgow West

Glasgow, United Kingdom

Location

Dept. of Medicine & Therapeutics, University of Leicester

Leicester, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 26721775 DERIVED

• 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.

  PMID: 17986694 DERIVED

MeSH Terms

Interventions

tezosentan

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2007
• First Posted: September 3, 2007
• Study Start: April 1, 2003
• Primary Completion: January 1, 2005
• Study Completion: January 1, 2005
• Last Updated: July 10, 2018

Record last verified: 2018-07

Locations

DE (5); AU (3); IT (2); CZ (5); US (16); GB (4); HU (4); NO (3)