Tezosentan in the Treatment of Acute Heart Failure

Acute Heart Failure Clinical Trial

— VERITAS 2  

Official title:

Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Study to Assess the Efficacy, Safety, and Tolerability of Tezosentan in Patients With Acute Heart Failure.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00524433
• Other study ID #: AC-051-307
• Status: Completed
• Phase: Phase 3
• Start date: April 2003
• Est. completion date: January 2005

Study information

• Verified date: July 2018
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 713
• Est. completion date: January 2005
• Est. primary completion date: January 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• 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)
• placebo

Locations

Country	Name	City	State
Australia	Concord Repatriation Hospital	Concord NSW
Australia	Alfred Hospital, Monash University, Central and Eastern School	Prahran	Victoria
Australia	Queen Elizabeth Hospital	Woodville SA
Czechia	Faculty Hospital St. Anna	Brno
Czechia	Krajska Nemocnice Liberec	Liberec
Czechia	Klinika Kardiologie IKEM	Prague
Czechia	University Hospital Vinohrady (FNKV)	Prague
Czechia	Masaryk Hospital	Usti nad Labem
Germany	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	Lubeck
Germany	Klinik u. Poliklinik F. Inn. Med. II, Univ. Klinik Regensburg	Regensburg
Hungary	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
Italy	Cattedra di Cardiologia, c/o Spedali Civili	Brescia
Italy	Istituto Clinico Humanitas, U.O. Cardiologia Clin. E Insuff. Cardiaca	Rozzano (MI)
Norway	Sentralsykehuset i More og Romsdal, Dept. of Cardiology	Alesund
Norway	Aker University Hospital, Div. Cardiology	Oslo
Norway	Central Hospital in Rogaland, Cardiology Division	Stavanger
United Kingdom	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 States	University Hospital	Augusta	Georgia
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Duke University Medical Center	Durham	North Carolina
United States	Elmhurst Hospital Center	Elmhurst	New York
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	Oracle Research	Huntsville	Alabama
United States	University of Iowa Hospital and Clinics	Iowa City	Iowa
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	USC Medical Center	Los Angeles	California
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	New York University School of Medicine	New York	New York
United States	Medical Research Institute	Slidell	Louisiana
United States	Baystate Medical Center-Cardiology Section	Springfield	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of death or worsening heart failure		within 7 days following study drug initiation
Secondary	Patient's dyspnea assessment, measured using a visual analog scale		Over first 24 hours