Heart DiseasesPhase 3NCT00458276
Study of the Efficacy and Safety of Tezosentan in Patients With Pre-operative Pulmonary Hypertension, Due to Left Heart Disease, Undergoing Open Heart Surgery
A Phase 3 study testing tezosentan in people with Heart Diseases and Hypertension, Pulmonary, run by Idorsia Pharmaceuticals Ltd. at 33 sites in 14 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Diseases, Hypertension, Pulmonary
- What is being tested?
- tezosentan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 274 participants
- Where
- 33 sitesin 14 countries
- Study dates
- Apr 2007to Mar 2008
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 11Show fewer
- 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
Trial locations and contacts
33 sites in 14 countries.
33 sites in 14 countries
United States9 sites
University of Virginia Health System
Charlottesville, Virginia, 22908
The Cleveland Clinic
Cleveland, Ohio, 44195
Baylor University Medical Center
Dallas, Texas, 75226
Duke University Medical Center
Durham, North Carolina, 27710
Texas Heart Institute/St. Luke's Episcopal Hospital/Baylor College
Houston, Texas, 77030
Columbia University Medical Center
New York, New York, 10032
Montefiore Medical Center/Albert Einstein College of Medicine
New York, New York, 10467
Stanford University School of Medicine
Stanford, California, 94305
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Canada5 sites
University of Alberta Hospital
Edmonton, Alberta, T6G2B7
London Health Sciences Centre-University Hospital
London, Ontario, N6A5A5
Montreal Heart Institute
Montreal, Quebec, H1T1C8
Quebec Heart Institute/Hopital Laval
Québec, Quebec, G1V4G5
Toronto General Hospital
Toronto, Ontario, M5G2C4
Germany3 sites
Deutches Herzzentrum
Berlin
Dresden Universitatsklinik/Cardiology Center
Dresden
Zentrum der Chirugie-Zchir-des Universitatsklinikums
Frankfurt, Main 60590
Austria2 sites
Medical University of Innsbruck
Innsbruck
AKH University of Vienna
Vienna
India2 sites
Narayana Hrudayalaya
Bangalore
Nizam's Institute of Medical Sciences
Hyderabaad
Italy2 sites
Fondazione IRCCS San Matteo Hospital, Cardiac Surgery
Pavia, 27100
Azienda Sanitaria Ospedaliera "San Giovanni Battista", Cardiac Surgery Division
Torino, 10126
Poland2 sites
Medical University of Silesia, 2nd Dept of Cardiac Surgery
Katowice
Klinika Chirurgii Serca, Naczyn I Transplantologii, Szpital Jana Pawla II
Krakow, 31-202
United Kingdom2 sites
Papworth Hospital
Cambridge
Northern General Hospital
Sheffield
Slovakia1 site
National Institute of Cardiovascular Diseases, Clinic of Heart Surgery
Bratislava
About this study
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
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.
Read the 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.
- Conditions
- Heart Diseases, Hypertension, Pulmonary
- Being tested
- tezosentan, placebo
- Keywords
- Left sided heart disease, Elevated pulmonary arterial pressure, Right ventricular failure, Cardiac surgery, heart-lung machine, cardiopulmonary bypass, tezosentan, Actelion
- Medical subject headings
- Heart Diseases, Hypertension, Pulmonary, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tezosentanDrug
Tezosentan (ACT-050089, Ro 61-0612) as a 1% solution in 0.9% NaCl (i.e., normal saline) for i.v. use.
placeboDrug
Placebo (i.e., normal saline) for i.v. use.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Tezosentan Receives: Drug: tezosentan |
| 2 | Placebo comparator | Placebo Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: During weaning from CPB
Secondary outcomes (3)
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
Measured: Within 28 days after study initiation
Time to weaning from cardiopulmonary bypass
Measured: Defined as time from release of cross-clamp to successful weaning from CPB
Time from end of CPB to final discharge from Intensive Care Unit (ICU)
Measured: From end of CPB to final discharge from ICU
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2007 (estimated)
- Study startApr 2007
- Primary completionFeb 2008
- Study completionMar 2008
Why it stopped: 6 month vital status report not collected after 28 day follow up analysis indicated no difference between placebo \& tezosentan
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 274 participants (actual)
Sponsor and investigators
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Andre Denault, Prof., Study chair, Montreal Heart InstituteRonald Pearl, MD, Study chair, Stanford UniversityRobert Michler, MD, Study chair, Montefiore Medical CenterSteven Tsui, Study chair, Papworth Hospital NHS Foundation TrustRainald Seitelberger, Prof., Study chair, AKH University of ViennaAndrea D'Armini, Prof., Study chair, San Matteo Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00458276
- Sponsor's protocol ID
- AC-051-350
- Status last verified
- Jul 2018
- First submitted
- 6 Apr 2007
- Last updated
- 9 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Denault AY, Pearl RG, Michler RE, Rao V, Tsui SS, Seitelberger R, Cromie M, Lindberg E, D'Armini AM. Tezosentan and right ventricular failure in patients with pulmonary hypertension undergoing cardiac surgery: the TACTICS trial. J Cardiothorac Vasc Anesth. 2013 Dec;27(6):1212-7. doi: 10.1053/j.jvca.2013.01.023. Epub 2013 Mar 21.
PubMed 23523254
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00458276
- Acronym / sponsor ID
- AC-051-350
- Conditions
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: 6 month vital status report not collected after 28 day follow up analysis indicated no difference between placebo \& tezosentan
- Enrolment
- 274 participants (actual)
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- Apr 2007
- Primary completion
- Feb 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 10 Apr 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: tezosentanTezosentan |
| 2 | Placebo comparator | Drug: placeboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (11 listed)
- Systolic blood pressure < 100 mmHg
- Significant chronic lung disease
- Emergency surgery
- Pregnant/breast-feeding
- Investigational drug use within 28 days prior to randomization
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tezosentanTezosentan (ACT-050089, Ro 61-0612) as a 1% solution in 0.9% NaCl (i.e., normal saline) for i.v. use. | Drug | 1 |
| placeboPlacebo (i.e., normal saline) for i.v. use. | Drug | 2 |
Primary outcome
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
3 secondary outcomes
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
Time to weaning from cardiopulmonary bypass
Time frame: Defined as time from release of cross-clamp to successful weaning from CPB
Time from end of CPB to final discharge from Intensive Care Unit (ICU)
Time frame: From end of CPB to final discharge from ICU
Results and safety
The study was stopped early (reason given: 6 month vital status report not collected after 28 day follow up analysis indicated no difference between placebo \& tezosentan). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2018.
- Derived from this study: PubMed 23523254Denault AY, Pearl RG, Michler RE, Rao V, Tsui SS, Seitelberger R, Cromie M, Lindberg E, D'Armini AM. Tezosentan and right ventricular failure in patients with pulmonary hypertension undergoing cardiac surgery: the TACTICS trial. J Cardiothorac Vasc Anesth. 2013 Dec;27(6):1212-7. doi: 10.1053/j.jvca.2013.01.023. Epub 2013 Mar 21.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andre Denault, Prof. study chair
Montreal Heart Institute
Ronald Pearl, MD study chair
Stanford University
Robert Michler, MD study chair
Montefiore Medical Center
33 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing tezosentan in people with Heart Diseases and Hypertension, Pulmonary, run by Idorsia Pharmaceuticals Ltd. at 33 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in United States, Canada, Germany, Austria, India and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: 6 month vital status report not collected after 28 day follow up analysis indicated no difference between placebo \& tezosentan). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00458276, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2018.