Clinical trial NCT03763045: Sildenafil in Hemodialysis Patients With Pulmonary Hypertension
Official title: Evaluation of the Effect of Sildenafil in Hemodialysis Patients With Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Pulmonary Hypertension
Hemodialysis Complication
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2018-12-04
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Sildenafil 25: Twenty hemodialysis patients will receive a dose of 25mg sildenafil daily for 3 months.

Sildenafil 50: Twenty hemodialysis patients will receive a dose of 50mg sildenafil daily for 3 months.

Placebo: Twenty hemodialysis patients will receive a placebo tablet daily for 3 months.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Decrease in Pulmonary Artery Pressure
timeFrame: 3 months
Secondary outcomes:
measure: Transthoracic echocardiography
timeFrame: 3 months
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain Shams University Hospital
state: Abbasia
Study officials:
affiliation: Associate Professor of Internal Medicine and Nephrology
name: Tamer W Elsaid, MD
role: STUDY_DIRECTOR
References: