Tezosentan in the Treatment of Acute Heart Failure

Phase 3

Completed

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

• Registration Number: NCT00524433
• 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: 2007-08-31
• Study First Posted: 2007-09-03
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-06
• Last Update Posted: 2018-07-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 713

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
2	placebo	-
1	tezosentan	tezosentan

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (42)

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

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