PDEI Following Mitral Valve Surgery in Patients With Pulmonary Hypertension

• ClinicalTrials.gov Identifier: NCT02378649
• Recruitment Status: Completed
• First Posted: March 4, 2015
• Last Update Posted: June 26, 2018
• Sponsor: Dr. Robert Klempfner Heart Rehabilitation Institute
• Information provided by (Responsible Party): Dr. Robert Klempfner Heart Rehabilitation Institute, Sheba Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pulmonary Hypertension; Mitral Valve Surgery	Drug: Sildenafil; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: March 2015
• Actual Primary Completion Date: June 2018
• Actual Study Completion Date: June 2018

Arms and Interventions

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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. 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.) [ Time Frame: 48 hours ]
   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

Secondary Outcome Measures :

1. Time on mechanical ventilation [ Time Frame: 96 hours ]
2. Total surgical intensive care time [ Time Frame: participants will be followed for the duration of ICU stay, an expected average of 4 days ]
   Duration of Surgical ICU stay
3. Change in functional capacity post operation (Change in NYHA functional class (optional 6MWT pre-discharge) [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 6 days ]
   Change in NYHA functional class (optional 6 minute walk test [6MWT] pre-discharge)
4. Study treatment related serious adverse events [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 6 days ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Israel

Cardiac Surgical Department, Leviev Heart Center

Ramat Gan, Tel Hashomer, Israel, 52621

Sponsors and Collaborators

Dr. Robert Klempfner Heart Rehabilitation Institute

More Information

• Responsible Party: Dr. Robert Klempfner Heart Rehabilitation Institute, Dr. Ferstenfeld Ido, Sheba Medical Center
• ClinicalTrials.gov Identifier: NCT02378649
• Other Study ID Numbers: 1839-14-SMC
• First Posted: March 4, 2015
• Last Update Posted: June 26, 2018
• Last Verified: June 2018

Keywords provided by Dr. Robert Klempfner Heart Rehabilitation Institute, Sheba Medical Center:

Pulmonary Hypertension

Additional relevant MeSH terms:

Hypertension, Pulmonary; Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Sildenafil Citrate; Vasodilator Agents; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Urological Agents