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Study of the Efficacy and Safety of Tezosentan in Patients With Pre-operative Pulmonary Hypertension, Due to Left Heart Disease, Undergoing Open Heart Surgery

Primary Purpose

Heart Diseases, Hypertension, Pulmonary

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

tezosentan

placebo

About this trial

This is an interventional treatment trial for Heart Diseases focused on measuring Left sided heart disease, Elevated pulmonary arterial pressure, Right ventricular failure, Cardiac surgery, heart-lung machine, cardiopulmonary bypass, tezosentan, Actelion

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Stanford University School of Medicine
Columbia University Medical Center
Montefiore Medical Center/Albert Einstein College of Medicine
Duke University Medical Center
Wake Forest University Health Sciences
The Cleveland Clinic
Baylor University Medical Center
Texas Heart Institute/St. Luke's Episcopal Hospital/Baylor College
University of Virginia Health System
Medical University of Innsbruck
AKH University of Vienna
University of Alberta Hospital
London Health Sciences Centre-University Hospital
Toronto General Hospital
Montreal Heart Institute
Quebec Heart Institute/Hopital Laval
Institute for Clinical and Experimental Medicine (IKEM)
Hopital Pitie Salpetriere
Deutches Herzzentrum
Dresden Universitatsklinik/Cardiology Center
Zentrum der Chirugie-Zchir-des Universitatsklinikums
Narayana Hrudayalaya
Nizam's Institute of Medical Sciences
Shaare Zedek Medical Center
Fondazione IRCCS San Matteo Hospital, Cardiac Surgery
Azienda Sanitaria Ospedaliera "San Giovanni Battista", Cardiac Surgery Division
Medical University of Silesia, 2nd Dept of Cardiac Surgery
Klinika Chirurgii Serca, Naczyn I Transplantologii, Szpital Jana Pawla II
Dedinje Cardiovascular Institute
National Institute of Cardiovascular Diseases, Clinic of Heart Surgery
Sahlgrenska University Hospital
Papworth Hospital
Northern General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

Tezosentan

Placebo

Outcomes

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.

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 to weaning from cardiopulmonary bypass

Time from end of CPB to final discharge from Intensive Care Unit (ICU)

Full Information

NCT ID

NCT00458276

First Posted

April 6, 2007

Last Updated

July 6, 2018

Sponsor

Idorsia Pharmaceuticals Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT00458276

Brief Title

Study of the Efficacy and Safety of Tezosentan in Patients With Pre-operative Pulmonary Hypertension, Due to Left Heart Disease, Undergoing Open Heart Surgery

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Terminated

Why Stopped

6 month vital status report not collected after 28 day follow up analysis indicated no difference between placebo & tezosentan

Study Start Date

April 2007 (undefined)

Primary Completion Date

February 2008 (Actual)

Study Completion Date

March 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Idorsia Pharmaceuticals Ltd.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Heart Diseases, Hypertension, Pulmonary

Keywords

Left sided heart disease, Elevated pulmonary arterial pressure, Right ventricular failure, Cardiac surgery, heart-lung machine, cardiopulmonary bypass, tezosentan, Actelion

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

274 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Tezosentan

Arm Title

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

tezosentan

Intervention Description

Tezosentan (ACT-050089, Ro 61-0612) as a 1% solution in 0.9% NaCl (i.e., normal saline) for i.v. use.

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

Placebo (i.e., normal saline) for i.v. use.

Primary Outcome Measure Information:

Title

Time Frame

During weaning from CPB

Secondary Outcome Measure Information:

Title

Time Frame

Within 28 days after study initiation

Title

Time to weaning from cardiopulmonary bypass

Time Frame

Defined as time from release of cross-clamp to successful weaning from CPB

Title

Time from end of CPB to final discharge from Intensive Care Unit (ICU)

Time Frame

From end of CPB to final discharge from ICU

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials: