PDEI Following Mitral Valve Surgery in Patients With Pulmonary Hypertension

Study Overview
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Brief Summary
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A randomized, placebo controlled, single center clinical trial for evaluation of efficacy and safety of Sildenafil administration in the cardiac ICU following Mitral Valve (MV) Surgery in patients with pre-operative Significant Pulmonary Hypertension.

Official Title
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A Randomized, Placebo Controlled, Single Center Clinical Trial for Evaluation of Efficacy and Safety of Sildenafil Administration in the Cardiac ICU Following Mitral Valve Surgery in Patients With Pulmonary Hypertension

Conditions
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Pulmonary Hypertension, Mitral Valve Surgery

Intervention / Treatment
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* Drug: Sildenafil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 22 Undergoing mitral valve surgery (either repair or replacement) with or without coronary revascularization, aortic valve replacement (AVR) or repair; or tricuspid valve surgery. Pre-operative pulmonary arterial systolic pressure >50 mm Hg as determined by resting echocardiography and post-operative sPAP > 45 mmHg as obtained from invasive hemodynamics measurements. Willing and able to give written informed consent prior to the procedure Exclusion Criteria: Hypersensitivity to study drug Women of child-bearing potential Expected need to administer nitrates that are clinically indicated peri-operatively Post-operative hypotension (systolic blood pressure (BP) <80) or evidence of shock (postoperative evidence of any kinds of shock) Cardiac or systemic amyloidosis Active malignancy other than BCC (basal cell carcinoma) Stable kidney dysfunction with Creatine clearence (CrCl) <30 mL/min during the screening period or hepatic failure other than mild Significant anemia (hemoglobin <8 mg/dl) preoperative. Known drug or alcohol dependence or any other factors which will interfere with the study conduct or interpretation of the results or in the opinion of the investigator are not suitable to participate; Any illness other than cardiac which might reduce life expectancy to less than 1 year from screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sildenafil<br>PDEI or placebo will be administered in the surgical ICU 4-6 hours after arriving from the Operative Room. The initial Dose will be 20mg X 3 NG and can be increase to 40mg X 3, it will be administered PO if the patient extubated. PDEI or placebo will continue up to 8 days or discharge. | Drug: Sildenafil<br>* Sildenafil administration in the cardiac ICU following Mitral Valve Surgery concomitant with best practice usual care<br>* Other names: Revatio \ Viagra;|
| Placebo Comparator: Placebo<br>PDEI or placebo will be administered in the surgical ICU 4-6 hours after arriving from the Operative Room. The initial Dose will be 20mg X 3 NG and can be increase to 40mg X 3, it will be administered PO if the patient extubated. PDEI or placebo will continue up to 8 days or discharge. | Drug: Placebo<br>* Placebo comparator concomitant with best practice usual care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate if sildenafil results in greater reduction in average mean pulmonary artery pressure (mPAP) compared to placebo. (Percent change in mPAP pressure at 48 hours as compared to the immediate post operative averages.) | Percent change in mPAP pressure at 48 hours as compared to the immediate post operative averages. Pulmonary pressures will be obtained through invasive hemodynamic measurements | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time on mechanical ventilation |  | 96 hours | 
| Total surgical intensive care time | Duration of Surgical ICU stay | participants will be followed for the duration of ICU stay, an expected average of 4 days | 
| Change in functional capacity post operation (Change in NYHA functional class (optional 6MWT pre-discharge) | Change in NYHA functional class (optional 6 minute walk test [6MWT] pre-discharge) | participants will be followed for the duration of hospital stay, an expected average of 6 days | 
| Study treatment related serious adverse events | Absence of serious adverse events related to study drug (shock, organ hypoperfusion, significant arrythmia and any other major event as defined by GCP guidelines) during hospital stay | participants will be followed for the duration of hospital stay, an expected average of 6 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Hypertension