Phosphodiesterase Type 5 Inhibitors in Patients With Group 2 Pulmonary Hypertension

The Efficacy of Phosphodiesterase Inhibitors in Patients With Group 2 Pulmonary Hypertension

The goal of this clinical trial is to test the efficacy of tadalafil in patients with group II pulmonary hypertension with CpcPH with elevated pulmonary vascular resistance (PVR equals or more than 4 WU).

The main question it aims to answer is:

• Can tadalafil improve patients with group II pulmonary hypertension with CpcPH, regarding functional, clinical, biomarker and echocardiographic outcomes? Participants will undergo right heart catheterization (RHC) to make sure they are fulfilling the inclusion criteria of CpcPH, then will be asked to take tadalafil 20 mg for two weeks then 40 mg if tolerated for 12 weeks, then participants will be followed up. Investigators will compare the drug group with the control group.

Study Overview

• Status: Completed
• Conditions: Group 2 Pulmonary Hypertension; CpcPH
• Intervention / Treatment: Drug: tadalafil 20 mg then 40 mg if tolerated

Detailed Description

The study aims at studying the efficacy of tadalafil in patients with group 2 pulmonary hypertension with elevated pulmonary vascular resistance guided by RHC. After fulfilling the inclusion criteria, investigators will recruit 48 patients, and do baseline echocardiography for comprehensive right ventricular (RV) study and 6 minute walk test, and then start tadalafil 20 mg then 4mg if tolerated, for 24 patients (drug group). After three months follow up, investigators will follow up the patients regarding RV function and the functional capacity, compared to matched control group.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Beni Suweif Governorate
    • Cairo, Beni Suweif Governorate, Egypt, 62511
      • Beni Suef University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• group 2 pulmonary hypertension with CpcPH with PVR equals or more than 4 by RHC.
• NYHA II-III symptoms.
• Patients should be on HF medical therapy 90 days before enrollment in the study.

Exclusion Criteria:

• All groups of PH, other than Group 2 PH.
• Patients with Group 2, but no meeting the predefined hemodynamic criteria for CpcPH (mean PAP more than 20 mmHg, mean PCWP more than 15 mmHg, PVR equals or more than 4 WU).
• Hypersensitivity, allergy, or intolerable side effects of PDE-5 inhibitors.
• Contraindication to PDE-5 inhibitors, including current nitrate therapy.
• Anticipated cardiac resynchronization therapy within 3 months of enrollment.
• History of heart transplant, ventricular-assist device, or any other solid-organ transplant
• Recent stroke, myocardial infarction, any coronary intervention; PCI or CABG.
• Decompensated heart failure.
• Female subject who is pregnant, breast-feeding, or unwilling to practice an acceptable method of birth control unless postmenopausal or sterile.
• Unreliability as a study participant, based on the investigator's (or designee's) knowledge of the subject (e.g., alcohol or other substance abuse, inability or unwillingness to adhere to the protocol, documented noncompliance, or vulnerable population)
• Current enrollment, or enrollment completed <30 days previously, in another investigational drug or device clinical study.
• Undergoing dialysis for end-stage renal disease.
• End-stage liver disease comorbidities, limiting exercise tolerance.
• Morbid obesity (body mass index > 40).
• Severe peripheral vascular disease with intermittent claudication.
• Status after amputation of lower extremity(s) at any level.
• Severe degenerative joint disease preventing normal walking.
• Cerebrovascular accident with long-term sequelae affecting ability to walk.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: tadalafil-receiving arm; Patients will take tadalafil for the 12 week period of follow up, in addition to the standard evidence-based therapy for the left heart disease.	Drug: tadalafil 20 mg then 40 mg if tolerated; Patients will receive tadalafil for 12 week follow up period
No Intervention: Tadalafil non-receiving arm; Patients will not take tadalafil for the 12 weeks follow up, only standard evidence-based therapy for the left heart disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional capacity	Six minute walk test, to assess the number of meters the patient can walk within 6 minutes, in be measured in meter unit.	12 weeks
Functional capacity	using NYHA classification either 1, 2, 3 or 4	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk profile assessment	Risk assessment by ESC/ERS multiparametric model, expressed as risk category (low, intermediate or high).	12 weeks
Rate of hospitalization	Rate of Heart failure- related hospitalization	12 weeks
Right ventricular size	using Echocardiography, by measuring - RV diameters (basal, mid cavity and longitudinal) in mm.	12 weeks
Right ventricular function	- Fractional area change (FAC) by echocardiography, in percentage (%) Time Frame: 12 weeks	12 weeks
Pulmonary artery pressure	Estimated pulmonary artery systolic pressure in mmHg (estimated from peak TR velocity, by echocardiography.	12 weeks
NT-proBNP	NT-proBNP by ELISA, in pg/mL	12 weeks
Right-sided heart failure manifestations	Peripheral edema grade (0 no edema to 4 severe edema)	12 weeks
Left ventricular diastolic function	E/e' ratio using doppler and tissue doppler echocardiography	12 weeks
Left ventricular systolic function	using modified simpsons method, by echocardiography, expressed in percentage (%)	12 weeks

Collaborators and Investigators

• Sponsor: Beni-Suef University
• Investigators: Study Director: Yasser Ahmed Abdelhady, Doctorate, Beni-Suef University

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2023
• Primary Completion (Actual): October 25, 2025
• Study Completion (Actual): October 25, 2025

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: April 1, 2024
• First Posted (Actual): April 5, 2024

Study Record Updates

• Last Update Posted (Actual): August 11, 2026
• Last Update Submitted That Met QC Criteria: August 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: CpcPH; right heart catheterization; pulmonary vascular resistance; PDEI
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indoles; Indole Alkaloids; Heterocyclic Compounds, 3-Ring; Carbolines; Tadalafil
• Other Study ID Numbers: FMBSUREC/06122022/ Zaher

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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