Sildenafil in Hemodialysis Patients With Pulmonary Hypertension

Phase 2

• Conditions: Pulmonary Hypertension; Hemodialysis Complication
• Interventions: Drug: Sildenafil; Other: Placebo

• Registration Number: NCT03763045
• Lead Sponsor: Ain Shams University

Brief Summary

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

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 Timeline

• Study First Submitted: 2018-11-07
• Study First Submitted QC: 2018-12-01
• Study Start: 2018-12-02
• Study First Posted: 2018-12-04
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-08
• Last Update Posted: 2019-01-09
• Primary Completion: 2019-02-16
• Study Completion: 2019-02-28

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sildenafil 25	Sildenafil	Twenty hemodialysis patients will receive a dose of 25mg sildenafil daily for 3 months.
Sildenafil 50	Sildenafil	Twenty hemodialysis patients will receive a dose of 50mg sildenafil daily for 3 months.
Placebo	Placebo	Twenty hemodialysis patients will receive a placebo tablet daily for 3 months.

Primary Outcome Measures

Name	Time	Method
Decrease in Pulmonary Artery Pressure	3 months	Decrease in ePAP (mmHg) via Doppler echocardiography Systolic right ventricular (or pulmonary artery)

Secondary Outcome Measures

Name	Time	Method
Transthoracic echocardiography	3 months	Decrease in Estimated PASP (Pulmonary Artery Systolic Pressure) in (mmHg).

Trial Locations

Locations (1)

Ain Shams University Hospital; 🇪🇬 Cairo, Abbasia, Egypt