Tezosentan in the Treatment of Acute Heart Failure (VERITAS 2)

• ClinicalTrials.gov Identifier: NCT00524433
• Recruitment Status: Completed
• First Posted: September 3, 2007
• Last Update Posted: July 10, 2018
• Sponsor: Idorsia Pharmaceuticals Ltd.
• Information provided by (Responsible Party): Idorsia Pharmaceuticals Ltd.

Tracking Information

• First Submitted Date: August 31, 2007
• First Posted Date: September 3, 2007
• Last Update Posted Date: July 10, 2018
• Study Start Date: April 2003
• Actual Primary Completion Date: January 2005 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 31, 2007): Incidence of death or worsening heart failure [ Time Frame: within 7 days following study drug initiation ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: August 31, 2007): Patient's dyspnea assessment, measured using a visual analog scale [ Time Frame: Over first 24 hours ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Tezosentan in the Treatment of Acute Heart Failure
• 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.
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Acute Heart Failure
• Acute Decompensation of Chronic 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)
• Drug: placebo

Study Arms

• Experimental: 1
  tezosentan
  Intervention: Drug: tezosentan
• Placebo Comparator: 2
  Intervention: Drug: placebo

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 31, 2007): 713
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: January 2005
• Actual Primary Completion Date: January 2005 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Czechia, Germany, Hungary, Italy, Norway, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT00524433
• Other Study ID Numbers: AC-051-307
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Idorsia Pharmaceuticals Ltd.
• Study Sponsor: Idorsia Pharmaceuticals Ltd.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Idorsia Pharmaceuticals Ltd.
• Verification Date: July 2018