- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00334490
Does Oral Sildenafil (Viagra) Decrease Mean Pulmonary Artery Pressure After Cardiac Surgery?
July 30, 2015 updated by: Unity Health Toronto
A Phase II, Double Blind Randomized Controlled Trial to Determine the Safety and Efficacy of 12.5mg of Oral Sildenafil (Viagra) Compared to Placebo to Decrease Pulmonary Hypertension in Cardiac Patients After Cardiopulmonary Bypass
Post-operative pulmonary hypertension is a risk factor for right ventricular failure and an increasing cause of morbidity and mortality in patients undergoing high-risk cardiac surgery.
Several treatments have been used to treat and reduce post operative pulmonary hypertension.
Unfortunately none of these treatments are approved for use in this condition and only one (inhaled nitric oxide) is specific enough to pulmonary hypertension to not cause dangerous low blood pressure in the rest of the body.
Sadly, inhaled nitric oxide is difficult and expensive to use, and can cause lung damage.
Sildenafil citrate is quite specific to the lung vessels, is easy to administer and does not easily cause low blood pressure in other areas of the body.
We hypothesize that oral sildenafil 12.5mg will decrease the baseline (pre-dose) mPAP by at least 20% compared with a placebo.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Sildenafil citarte is a selective pulmonary vasodilator without profound effects on systemic hemodynamics making it an attractive option for treating post operative pulmonary hypertension in the cardiac surgical patients.
It is inexpensive and feasible to administer.
Intravenous as well as oral doses have been shown to reduce the mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in animal models as well as in clinical trials with adults with primary pulmonary hypertension and children after cardiac surgery .
However, no data exists to support the safety and efficacy of Sildenafil citrate in the adult cardiac surgical population.
The purpose of this study is to further investigate the potential role of Sildenafil citrate to treat post operative pulmonary hypertension in the cardiac population.
Study Type
Interventional
Enrollment (Actual)
40
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M5B 1W8
- St. Michael's Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 18 years of age or older
- Scheduled for or has recently undergone a primary or re-do cardiac surgical procedure including coronary artery bypass graft surgery (CABG), heart valve replacement or repair, ascending aortic replacement or repair or any combinations of these procedures with CPB
- No documented allergy to sildenafil citrate
- No clinical or laboratory evidence on routine blood work of significant renal disease or failure. (requires dialysis or a creatinine >/= 200umol/L)
- No clinical or documented laboratory evidence on routine blood work of hepatic disease or failure. (ALT or AST 5x upper limit of normal (ULN) or jaundice)
- The patient if female and of child bearing age is not known to be pregnant.
- No documented history of severe chronic respiratory disease defined as an FEV/VC1< 50% predicted.
- Not currently enrolled as an active participant in another clinical trial of a medical therapy or device.
- No documented stroke or transient ischemic attack within 6 months of study participation
- No documented critical carotid artery stenosis (>70%)
- No retinitis pigmentosa.
- The patient has authorized his/her consent to participate in this trial pre-operatively OR consent to participation is granted on the patient's behalf by a substitute decision maker pre or post operatively.
POST-OPERATIVELY
- A pulmonary arterial catheter (swan-ganz catheter) is insitu.
- The patient has a mPAP measurement of >/= 25mmHg for at least 1 hour.
- The patient has a mean arterial pressure (MAP) of >/= 65mmHg.
- The patient has a heart rate of greater than 40 and less than 130 beats/minute.
- The patient is intubated and mechanically ventilated as per standard ventilation protocol at St. Michael's Hospital.
- The patient has not received intravenous nitroglycerin or nitroprusside within 1 hour before treatment with study medication.
Exclusion Criteria:
POST-OPERATIVELY
- The patient requires nitroglycerin based medications continuously (topical/oral/intravenous)
- The patient has an arterial pH of < 7.30 or ≥ 7.47
- The patient has clinical and or documented laboratory evidence from routine blood work of renal dysfunction or failure. (Doubling of pre-operative creatinine or requiring dialysis is indicative of renal dysfunction.)
- The patient has clinical and or documented laboratory evidence from routine blood work of significant hepatic disease or failure. (ALT or AST 5 times ULN or obvious jaundice will be indicative of liver dysfunction)
- The patient's current medical condition in the opinion of the investigator and/or the patient's attending ICU physician makes him/her inappropriate for participation in this study.
- The patient is currently a participant in a clinical trial of an investigational therapy including a drug or medical device.
- The patient has clinical indications of sepsis defined as 2 of the following five criteria: i) leukocytosis (or) leukopenia: wbc >12 x 109/L (or) <4x109/L (>10% bands also, ii) fever (or) hypothermia (temp >38.5C or <36C), iii) tachycardia, hr > 90 beats/minute, iv) tachypnea, respiratory rate (RR) >18 breaths/minute, v) hypotension, SBP <90 mmHg
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 1
Oral Sildenafil 12.5 mg
|
12.5 mg Sildenafil once with optional second dose
Other Names:
12.5 mg orally once with optional second dose
Other Names:
|
Placebo Comparator: 2
Placebo in 5 mls distilled water
|
Oral Placebo in 5 mls distilled water
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To determine the efficacy of 12.5mg oral sildenafil to decrease the mPAP in patients presenting with a mPAP >/= 25mmHg after cardiopulmonary bypass.
Time Frame: Begining 2 hours postoperatively through 75 minutes post dosing
|
Begining 2 hours postoperatively through 75 minutes post dosing
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To determine the efficacy of a second dose of oral sildenafil 12.5mg to decrease the mPAP in those patients who do not respond with a 20% decrease in mPAP after the initial administration of study medication.
Time Frame: From post operative dosing through to hospital discharge
|
From post operative dosing through to hospital discharge
|
To determine the safety of oral sildenafil to treat increased mPAP after cardiac surgery.
Time Frame: Begining 2 hours postoperatively through discharge from the hospital
|
Begining 2 hours postoperatively through discharge from the hospital
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: David Mazer, MD, Unity Health Toronto
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2005
Primary Completion (Actual)
April 1, 2009
Study Completion (Actual)
May 1, 2009
Study Registration Dates
First Submitted
June 6, 2006
First Submitted That Met QC Criteria
June 6, 2006
First Posted (Estimate)
June 7, 2006
Study Record Updates
Last Update Posted (Estimate)
July 31, 2015
Last Update Submitted That Met QC Criteria
July 30, 2015
Last Verified
July 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Respiratory Tract Diseases
- Lung Diseases
- Hypertension
- Hypertension, Pulmonary
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Urological Agents
- Enzyme Inhibitors
- Phosphodiesterase Inhibitors
- Phosphodiesterase 5 Inhibitors
- Sildenafil Citrate
Other Study ID Numbers
- 091532
- REB 04-093 (Other Identifier: St Michael's Hospital, Toronto)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Pulmonary Hypertension
-
Sheffield Teaching Hospitals NHS Foundation TrustUniversity of SheffieldCompletedIdiopathic Pulmonary Arterial Hypertension | Chronic Thromboembolic Pulmonary HypertensionUnited Kingdom
-
Centre Chirurgical Marie LannelongueUnknownChronic Thrombo-embolic Pulmonary Hypertension and Pulmonary Arterial HypertensionFrance
-
BayerCompletedPrimary HypertensionChina
-
Heidelberg UniversityMerck Sharp & Dohme LLCRecruitingChronic Thromboembolic Pulmonary Hypertension | Primary Pulmonary Arterial HypertensionGermany
-
University of South FloridaWithdrawnPulmonary Arterial Hypertension | Familial Primary Pulmonary Hypertension | Idiopathic Pulmonary Arterial Hypertension | Primary Pulmonary HypertensionUnited States
-
Papworth Hospital NHS Foundation TrustMerck Sharp & Dohme LLCCompleted
-
University of Kansas Medical CenterRecruitingPulmonary Arterial Hypertension | Pulmonary Hypertension | Chronic Thromboembolic Pulmonary Hypertension | Pulmonary Hypertension Due to Left Heart Disease | Pulmonary Hypertension, Primary, 4 | Pulmonary Hypertension, Primary, 2 | Pulmonary Hypertension, Primary, 3 | Pulmonary Hypertension, Primary and other conditionsUnited States
-
Vanderbilt University Medical CenterJohns Hopkins UniversityCompletedPulmonary Arterial Hypertension | Idiopathic Pulmonary Arterial Hypertension | Associated Pulmonary Arterial Hypertension | Heritable Pulmonary Arterial HypertensionUnited States
-
University of ZurichCompletedPulmonary Hypertension | Pulmonary Artery Hypertension | Chronic Thromboembolic Pulmonary HypertensionSwitzerland
-
University of ZurichActive, not recruitingPulmonary Artery Hypertension | Chronic Thromboembolic Pulmonary Hypertension | Pulmonary Vascular DisorderSwitzerland
Clinical Trials on Sildenafil
-
University of PennsylvaniaWalter Reed National Military Medical CenterRecruiting
-
Duke UniversityNational Heart, Lung, and Blood Institute (NHLBI); PfizerCompleted
-
Rambam Health Care CampusUnknown
-
Pfizer's Upjohn has merged with Mylan to form Viatris...CompletedErectile DysfunctionSingapore
-
Northwestern UniversityCompletedHand Foot Skin ReactionUnited States
-
The Cleveland ClinicCompletedPulmonary Hypertension | Diffuse Parenchymal Lung DiseaseUnited States
-
Pfizer's Upjohn has merged with Mylan to form Viatris...Completed
-
iX Biopharma Ltd.Linear Clinical ResearchCompletedErectile DysfunctionAustralia
-
Rigshospitalet, DenmarkGlostrup University Hospital, CopenhagenCompletedBecker Muscular DystrophyDenmark
-
N4 Pharma UK Ltd.BDD Pharma LtdCompleted