Tezosentan in Acute Heart Failure

Acute Heart Failure Clinical Trial

— VERITAS 1  

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: NCT00525707
• Other study ID #: AC-051-306
• 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: 735
• 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 4ML/h (1 mg/h) for 23.5 to 71.5 h (24 to 72 h in total)

Locations

Country	Name	City	State
Austria	AKH University of Vienna, Abt. Medizinische Kardiologie	Vienna
Denmark	Roskilde Amt Sygehus	Roskilde
France	Hopital Ambroise Pare, Service de Cardiologie	Boulogne
France	Heart Failure clinic C.H. Dubos	Pontoise
France	Hopitaux Universitaires de Strasbourg, Hopital Hautepierre	Strasbourg
France	CHU Rangueil, Cardiologie A	Toulouse
Germany	Medizinische Klinik I, Universitatsklinikum Aachen	Aachen
Germany	Campus Virchow-Klinikum, Medizinishe Klinik mit Schwerpunkt Kardiologie	Berlin
Germany	Georg-August-Universitat Gottingen, Zentrum fur Innere Med	Gottingen
Greece	Dept. of Cardiology, University of Athens, Alexandra Hospital	Athens
Israel	Barzilai Hospital	Ashkelon
Israel	Carmel Medical Center	Haifa
Israel	Wolfson Medical Center	Holon
Israel	Hadassah Hospital	Jerusalem
Israel	Nazareth Hospital EMMS	Nazareth
Israel	Assaf-Harofeh Medical Center	Zerifin
Poland	Klinika Kardiologii i Chorob Wewnetrznych, Samodzielny Publiczny Szpital	Bydgoszcz
Poland	Klinika Chorob Serca, Akademia Medyczna w Gdansku	Gdansk
Poland	I Klinika Kardiolgii, Collegium Medicum UJ	Krakow
Poland	Institute of Cardiology College, College of Medicine of Jagellonian University	Krakow
Poland	Kategra I Klinika Kardiolgii AM	Wroclaw
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne
Switzerland	Cardio Centro Ticino, Servizio Cardiovasculare	Lugano
Switzerland	University Hospital Zurich	Zurich
United Kingdom	Glasgow Royal Infirmary	Glasgow
United Kingdom	Hull Royal Infirmary	Kingston Upon Hull
United Kingdom	Scunthorpe General Hospital	Scunthorpe
United States	Medical Associates, Bellebue	Bellevue	Washington
United States	University of Alabama-Birmingham	Birmingham	Alabama
United States	Danville Medical Center	Danville	Virginia
United States	Denver VAMC	Denver	Colorado
United States	Veterans Affairs Medical Center	Houston	Texas
United States	Advanced Heart Failure and Transplant Service, Palo Alto VA Health Care System, Cardiology Section	Palo Alto	California
United States	The Heart Hospital at Alledgheny General, Division of Cardiology	Pittsburgh	Pennsylvania
United States	Tyler Cardiovascular Consultants	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Countries where clinical trial is conducted

United States,  Austria,  Denmark,  France,  Germany,  Greece,  Israel,  Poland,  Switzerland,  United Kingdom, 

Outcome

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