Sildenafil in Hemodialysis Patients With Pulmonary Hypertension

Evaluation of the Effect of Sildenafil in Hemodialysis Patients With Pulmonary Hypertension

Sildenafil is a phosphodiesterase inhibitor that can exert a nitric oxide-mediated vasodilation effect, so it's considered one of the preferred agents especially in hypoxia induced pulmonary hypertension, can achieve pulmonary vasodilation by enhancing sustained levels of cyclic guanosine monophosphate (cGMP) and nitric oxide.

Despite the potential burden of pulmonary hypertension in hemodialysis patients, such agent like sildenafil has limited studies about optimum dose, safety and long term efficacy in End stage renal disease patients on hemodialysis with pulmonary hypertension

Study Overview

• Status: Unknown
• Conditions: Hemodialysis Complication; Pulmonary Hypertension
• Intervention / Treatment: Drug: Sildenafil; Drug: Sildenafil; Other: Placebo

Detailed Description

1- To evaluate the effect of sildenafil on pulmonary artery pressure and right ventricular function in hemodialysis patients with pulmonary hypertension.

1. Primary outcome:

   ● Reduction in estimated Pulmonary Artery pressure value (ePAP) in mmHg via transthoracic Doppler Echocardiography.

2. Secondary outcomes:

   • Detection of safety of sildenafil in hemodialysis patients.
   • Finding out sildenafil's optimum dose for hemodialysis patients with pulmonary hypertension.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Abbasia
    • Cairo, Abbasia, Egypt, 00202
      • Ain Shams University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age from 18-80 years old.
2. Patients on maintenance hemodialysis for more than six months receiving 3 sessions / week using bicarbonate dialysate with a low flux filter and heparin as anticoagulant.
3. Estimated Pulmonary Artery Pressure (ePAP) ≥35 mmHg via Doppler echocardiography
4. Urea reduction ratio (URR) will be ≥ 60% for all patients.
5. Dry weight will be targeted in each case to achieve edema-free state.
6. Informed consent in accordance with the Declaration of Helsinki.

Exclusion Criteria:

• 1. Current treatment of pulmonary hypertension (prostacyclin analogues, endothelin receptor antagonists or phosphodiesterase inhibitors).

  2-Heart diseases (congestive heart failure, ischemic heart disease, congenital heart disease).

  3- Lung diseases (chronic obstructive pulmonary disease, pulmonary thromboemboli or tumor, interstitial lung diseases, sleep apnea, pulmonary fibrosis, Sarcoidosis).

  4-Systemic diseases (scleroderma, systemic lupus erythematosus, portal hypertension).

  5-Human immunodeficiency virus (HIV) infection. 6-History of hypersensitivity to sildenafil. 7-Treatment with any drugs that may interact with sildenafil (Erythromycin , Azoles, Saquinavir-CYP3A4 inhibitors- , Bosentan - CYP3A4 inducer-Nitrates ) 8- Uncontrolled hypertension 9- Anemia with hemoglobin level <10 g/dl

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sildenafil 25; Twenty hemodialysis patients will receive a dose of 25mg sildenafil daily for 3 months.	Drug: Sildenafil; Sildenafil 25 mg: Phosphodiesterase inhibitor to be taken once daily; Drug: Sildenafil; Sildenafil 50 mg: Phosphodiesterase inhibitor to be taken once daily
Experimental: Sildenafil 50; Twenty hemodialysis patients will receive a dose of 50mg sildenafil daily for 3 months.	Drug: Sildenafil; Sildenafil 25 mg: Phosphodiesterase inhibitor to be taken once daily; Drug: Sildenafil; Sildenafil 50 mg: Phosphodiesterase inhibitor to be taken once daily
Placebo Comparator: Placebo; Twenty hemodialysis patients will receive a placebo tablet daily for 3 months.	Other: Placebo; Placebo tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in Pulmonary Artery Pressure	Decrease in ePAP (mmHg) via Doppler echocardiography Systolic right ventricular (or pulmonary artery)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transthoracic echocardiography	Decrease in Estimated PASP (Pulmonary Artery Systolic Pressure) in (mmHg).	3 months

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Study Director: Tamer W Elsaid, MD, Associate Professor of Internal Medicine and Nephrology

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2018
• Primary Completion (Anticipated): February 16, 2019
• Study Completion (Anticipated): February 28, 2019

Study Registration Dates

• First Submitted: November 7, 2018
• First Submitted That Met QC Criteria: December 1, 2018
• First Posted (Actual): December 4, 2018

Study Record Updates

• Last Update Posted (Actual): January 9, 2019
• Last Update Submitted That Met QC Criteria: January 8, 2019
• Last Verified: January 1, 2019

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: Med135

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No