Combination Therapy of Tadalafil 2.5mg Plus Sildenafil 25mg Versus Tadalafil 5 mg Monotherapy for Treatment of Erectile Dysfunction: A Randomized, Placebo-Controlled Double-Blinded Cross-Over Study

Erectile dysfunction (ED) is characterized by the persistent inability to attain or sustain an erection adequate for satisfactory sexual intercourse. As one of the most common male sexual health disorders, ED exhibits a global prevalence of moderate-to-severe cases ranging between 5% and 20% (1). Although erectile dysfunction is not life-threatening, it can substantially impair both physical and psychosocial well-being, exerting a notable negative impact on the quality of life of affected individuals and their partners.

ED is a multifactorial condition associated with vascular, psychological, and, in some cases, idiopathic causes (2). Management strategies encompass lifestyle modification, pharmacotherapy particularly with phosphodiesterase type 5 (PDE5) inhibitors, vacuum erection devices, intracavernosal injections, and surgical options (1). ED frequently coexists with metabolic and cardiovascular disorders and shows a rising incidence with advancing age and the presence of cardiovascular risk factors (2). Both physiological and psychological mechanisms may underlie the condition; psychological etiologies tend to be more prevalent in younger, otherwise healthy individuals (3). The presence of preserved nocturnal erections is a key clinical indicator suggestive of a psychogenic origin of ED (4).

Phosphodiesterase-5 inhibitors (PDE5Is) represent the primary pharmacologic therapy for ED. Currently, seven PDE5Is (avanafil, lodenafil, mirodenafil, sildenafil, tadalafil, udenafil, and vardenafil) are available in varying dosages and formulations. Their efficacy has been consistently demonstrated in randomized controlled trials (5)(6).

Sildenafil exhibits a rapid onset of action, typically beginning 30 minutes after administration, with an effective duration of 4 to 6 hours and a maximum pharmacological activity lasting up to 12 hours (7). While sildenafil is effective in managing erectile dysfunction, discontinuation rates among responders range from 20% to 50% (8). In contrast, tadalafil, a selective and long-acting PDE5 inhibitor introduced in 2003, has a slightly faster onset around 20 minutes and is recommended to be taken at least 30 minutes before sexual activity. Notably, tadalafil has the longest duration of action among PDE5 inhibitors, with effects lasting up to 72 hours. Approximately 52% of patients are able to achieve successful intercourse within 30 minutes of ingestion (9). The purpose of this study is to evaluate the efficacy and safety of Tadalafil 2.5 mg plus sildenafil 25 mg as a combination therapy versus tadalafil 5 mg monotherapy for Treatment of Erectile Dysfunction

Study Overview

• Status: Not yet recruiting
• Conditions: Erectile Dysfunction
• Intervention / Treatment: Drug: Tadalafil 2.5 mg; Drug: Sildenafil 25 mg; Drug: Tadalafil 5 mg

• Study Type: Interventional
• Enrollment (Estimated): 142
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• -Men aged 18-70 years with a clinical diagnosis of erectile dysfunction (ED) for ≥3 months.
• International Index of Erectile Function (IIEF-5) score ≤21.
• Stable sexual relationship for ≥3 months.
• Willingness to adhere to the study protocol and provide informed consent.
• No prior use of PDE5 inhibitors within 4 weeks before enrollment.

Exclusion Criteria:

• -Severe cardiovascular disease (uncontrolled hypertension, recent MI/stroke).
• Hypersensitivity to tadalafil, sildenafil, or any PDE5 inhibitor.
• Severe hepatic/renal impairment (e.g., CrCl <30 mL/min, Child-Pugh C).
• Concomitant use of nitrates, strong CYP3A4 inhibitors (e.g., ritonavir, ketoconazole).
• History of priapism, penile deformities, or radical prostatectomy.
• Major psychiatric disorders affecting compliance.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1; patients recived Tadalafil 2.5 mg + Sildenafil 25 mg.	Drug: Tadalafil 2.5 mg; patients recived Tadalafil 2.5 mg daily; Drug: Sildenafil 25 mg; patients recived Sildenafil 25 mg daily
Active Comparator: Group2; patients recived Tadalafil 5 mg monotherapy	Drug: Tadalafil 5 mg; patients recived Tadalafil 5 mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Erectile Function (IIEF-5 Score)	Change in Erectile Function (IIEF-5 Score)	12 week

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 10, 2025
• First Submitted That Met QC Criteria: September 10, 2025
• First Posted (Estimated): September 16, 2025

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 19, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Mental Disorders; Genital Diseases, Male; Male Urogenital Diseases; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Erectile Dysfunction; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amides; Indoles; Purines; Indole Alkaloids; Sulfonamides; Sulfones; Heterocyclic Compounds, 3-Ring; Piperazines; Carbolines; Sildenafil Citrate; Tadalafil
• Other Study ID Numbers: Tadal+Silden VSTadal ED

Drug and device information, study documents

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