PDEI Following Mitral Valve Surgery in Patients With Pulmonary Hypertension

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Hypertension; Mitral Valve Surgery
• Intervention / Treatment: Drug: Sildenafil; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Tel Hashomer
    • Ramat Gan, Tel Hashomer, Israel, 52621
      • Cardiac Surgical Department, Leviev Heart Center

Participation Criteria

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:

1. Age ≥ 22
2. Undergoing mitral valve surgery (either repair or replacement) with or without coronary revascularization, aortic valve replacement (AVR) or repair; or tricuspid valve surgery.
3. 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.
4. Willing and able to give written informed consent prior to the procedure

Exclusion Criteria:

1. Hypersensitivity to study drug
2. Women of child-bearing potential
3. Expected need to administer nitrates that are clinically indicated peri-operatively
4. Post-operative hypotension (systolic blood pressure (BP) <80) or evidence of shock (postoperative evidence of any kinds of shock)
5. Cardiac or systemic amyloidosis
6. Active malignancy other than BCC (basal cell carcinoma)
7. Stable kidney dysfunction with Creatine clearence (CrCl) <30 mL/min during the screening period or hepatic failure other than mild
8. Significant anemia (hemoglobin <8 mg/dl) preoperative.
9. 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;
10. Any illness other than cardiac which might reduce life expectancy to less than 1 year from screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sildenafil; 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; Sildenafil administration in the cardiac ICU following Mitral Valve Surgery concomitant with best practice usual care; Other Names: Revatio \ Viagra
Placebo Comparator: Placebo; 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; Placebo comparator concomitant with best practice usual care

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dr. Robert Klempfner Heart Rehabilitation Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: February 5, 2015
• First Submitted That Met QC Criteria: February 26, 2015
• First Posted (Estimate): March 4, 2015

Study Record Updates

• Last Update Posted (Actual): June 26, 2018
• Last Update Submitted That Met QC Criteria: June 24, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension
• 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: 1839-14-SMC