Study of the Efficacy and Safety of Tezosentan in Patients With Pre-operative Pulmonary Hypertension, Due to Left Heart Disease, Undergoing Open Heart Surgery
This study has been terminated.
(6 month vital status report not collected after 28 day follow up analysis indicated no difference between placebo & tezosentan)
Sponsor:
Actelion
Information provided by:
Actelion
ClinicalTrials.gov Identifier:
NCT00458276
First received: April 6, 2007
Last updated: February 11, 2010
Last verified: February 2010
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Purpose
Endothelin-1 is a powerful substance that may be involved in causing hemodynamic instability (problems related to unstable blood pressure) during and after open heart surgery. Tezosentan is an investigational intravenous drug that blocks the endothelin receptors. This clinical trial will assess the potential benefit of tezosentan compared with placebo in the treatment of patients undergoing open heart surgery with cardiopulmonary bypass (CPB). Treatment time is from the start of surgery up to 24 hours.
| Condition | Intervention | Phase |
|---|---|---|
|
Heart Diseases Hypertension, Pulmonary |
Drug: tezosentan Drug: placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Assess the Efficacy, Safety and Tolerability of Tezosentan in Patients With Pre-operative Pulmonary Hypertension, Due to Left Heart Disease, Undergoing Cardiac Surgery |
Resource links provided by NLM:
Further study details as provided by Actelion:
Primary Outcome Measures:
- The primary objective of this trial is to demonstrate that tezosentan, a dual ERA, reduces the incidence of clinically relevant right ventricular failure in patients with pre-operative pulmonary hypertension, due to left heart disease, undergoing CPB. [ Time Frame: During weaning from CPB ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Proportion of patients w/a major clinical event w/in 28 days after study drug initiation like death/major cardiovascular events/infections that prolong hospital stay or require re-admission/new onset of renal failure requiring renal replacement therapy [ Time Frame: Within 28 days after study initiation ] [ Designated as safety issue: No ]
- Time to weaning from cardiopulmonary bypass [ Time Frame: Defined as time from release of cross-clamp to successful weaning from CPB ] [ Designated as safety issue: No ]
- Time from end of CPB to final discharge from Intensive Care Unit (ICU) [ Time Frame: From end of CPB to final discharge from ICU ] [ Designated as safety issue: No ]
| Enrollment: | 274 |
| Study Start Date: | April 2007 |
| Study Completion Date: | March 2008 |
| Primary Completion Date: | February 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 1
Tezosentan
|
Drug: tezosentan
Tezosentan (ACT-050089, Ro 61-0612) as a 1% solution in 0.9% NaCl (i.e., normal saline) for i.v. use.
|
|
Placebo Comparator: 2
Placebo
|
Drug: placebo
Placebo (i.e., normal saline) for i.v. use.
|
Detailed Description:
Endothelin-1 levels are increased during and after cardiac surgery with cardiopulmonary bypass (CPB), and are associated with many deleterious consequences, including increased pulmonary arterial pressure (PAP), increased pulmonary vascular resistance (PVR), reduced myocardial contractility, and ultimately right ventricular failure. Right ventricular failure during weaning from CPB increases the risk of mortality and morbidity, especially in patients with elevated PAP prior to cardiac surgery. Endothelin receptor antagonists (ERAs) have been shown to decrease PVR and pulmonary arterial pressure (PAP), and improve right ventricular function in patients with pulmonary arterial hypertension. In animal models, ERAs have been shown to decrease the incidence of post-bypass pulmonary hypertensive crises. The primary objective of this trial is to demonstrate that tezosentan, a dual ERA, reduces the incidence of clinically relevant right ventricular failure in patients with pre-operative pulmonary hypertension, due to left heart disease, undergoing CPB.
Eligibility| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patients ≥ 18 years of age
- Male or female patients (females of child-bearing potential must have been surgically sterilized or use a reliable method of contraception).
- Patients undergoing complex* cardiac surgery on CPB and having systolic PAP > 40 mmHg or mean PAP > 30 mmHg (*surgery on 2 valves, 1 valve and revascularization, or reoperation of a valve)
- Patients undergoing cardiac surgery on CPB and having pre-operative pulmonary hypertension due to left heart disease with systolic PAP > 60 mmHg
- Signed written informed consent
Exclusion Criteria:
- Systolic blood pressure < 100 mmHg
- Significant chronic lung disease
- Emergency surgery
- Pregnant/breast-feeding
- Investigational drug use within 28 days prior to randomization
- Complex adult congenital heart disease.
- Severe concomitant illness limiting life expectancy to < 6 months
- Participation in a device study that will affect the outcome of the study
- Pre-operative use of balloon pump, inotropes/vasopressors, treatment of pulmonary arterial hypertension
- Known hypersensitivity to tezosentan or drugs of the same class, or any of their excipients
- Severe liver impairment
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00458276
Show 33 Study Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00458276
Show 33 Study Locations
Sponsors and Collaborators
Actelion
Investigators
| Study Chair: | Andre Denault, Prof. | Montreal Heart Institute |
| Study Chair: | Ronald Pearl, MD | Stanford University |
| Study Chair: | Robert Michler, MD | Montefiore Medical Center |
| Study Chair: | Steven Tsui | Papworth Hospital |
| Study Chair: | Rainald Seitelberger, Prof. | AKH University of Vienna |
| Study Chair: | Andrea D'Armini, Prof. | San Matteo Hospital |
More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Elisabet Lindberg, MD, International Clinical Leader, Actelion |
| ClinicalTrials.gov Identifier: | NCT00458276 History of Changes |
| Other Study ID Numbers: | AC-051-350 |
| Study First Received: | April 6, 2007 |
| Last Updated: | February 11, 2010 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Actelion:
|
Left sided heart disease Elevated pulmonary arterial pressure Right ventricular failure Cardiac surgery |
heart-lung machine cardiopulmonary bypass tezosentan Actelion |
Additional relevant MeSH terms:
|
Heart Diseases Hypertension Hypertension, Pulmonary Vascular Diseases Cardiovascular Diseases Lung Diseases |
Respiratory Tract Diseases Tezosentan Epoprostenol Vasodilator Agents Antihypertensive Agents Platelet Aggregation Inhibitors |
ClinicalTrials.gov processed this record on September 26, 2016