Daily tadalafil plus as-needed sildenafil for men whose ED did not respond to PDE5 inhibitors

Daily Tadalafil 5 mg Combined With On-Demand Sildenafil 100 mg for Treatment of Erectile Dysfunction in PDE-5I Non Responder Patients: A Multicenter Randomized, Double-Blind, Placebo-Controlled Trial

This tests whether taking tadalafil 5 mg every day together with sildenafil 100 mg as needed helps men with erectile dysfunction who did not respond to PDE5 inhibitors alone.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 500 (estimated)
• Ages: 21 Years and up
• Sex: Male
• Sponsor: Mansoura University (other)
• Drugs / interventions: radiation
• Locations: 11 sites (Al Mansurah, Dakahlia Governorate and 10 other locations)
• Trial ID: NCT07391579 on ClinicalTrials.gov

What this trial studies

This phase 4, randomized interventional study enrolls men with at least six months of erectile dysfunction who failed to respond to maximum-dose PDE5 inhibitors. Participants are randomly assigned to daily tadalafil 5 mg plus on-demand sildenafil 100 mg or daily placebo plus on-demand sildenafil 100 mg, with baseline exams and lab testing before treatment. The main efficacy outcome is change in erectile function measured by the IIEF-EF domain, and safety/tolerability are monitored throughout. The trial is conducted at multiple university urology centers in Egypt.

Who should consider this trial

Good fit: Sexually active adult men with ED for ≥6 months, IIEF-EF score <17, documented non-response to maximum-dose PDE5 inhibitors on at least four occasions, and a stable sexual relationship of ≥6 months are the intended participants.

Not a fit: Men with penile anatomical deformities or prior penile surgery, active malignancy or severe systemic illness, contraindications to PDE5 inhibitors (including nitrate use or high cardiac risk), or current alternative ED treatments are excluded and unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could restore erectile function and improve sexual satisfaction for men who previously did not respond to PDE5 inhibitors alone.

How similar studies have performed: Smaller clinical reports and clinical experience suggest switching or combining PDE5 inhibitors can help some non-responders, but large randomized evidence is limited.

Eligibility criteria

Inclusion Criteria:

* Sexually active male.
* History of ED for ≥6 months.
* Erectile function domain of IIEF-15 score \<17.
* Documented failure to respond to PDE-5I \[definition of non-responder patients are patients with ED who don't respond to maximum dose of PDE-5I on ≥4 occasions in spite of accurate timing and good sexual stimulation\].
* Stable sexual relationship ≥ 6 months.

Exclusion Criteria:

* Penile anatomical deformities or Peyronie's disease.
* Pelvic surgery or radiation.
* Active malignancy or severe systemic illness.
* Previous penile surgery of any kind, such as penile prosthesis, penile lengthening, penile cancer surgery, penile plication or grafting.
* Contraindication to PDE5i (High risk cardiac patients, patients on nitrates, hypotension).
* Using other treatments for ED e.g., Intra-cavernoasl prostaglandin injection therapy.

Where this trial is running

Al Mansurah, Dakahlia Governorate and 10 other locations

• Urology and Nephrology Center, Mansoura University — Al Mansurah, Dakahlia Governorate, Egypt (RECRUITING)
• Faculty of medicine, Alexandria University — Alexandria, Egypt (RECRUITING)
• Faculty of medicine, Aswan university — Aswān, Egypt (RECRUITING)
• Faculty of Medicine - Assiut University — Asyut, Egypt (RECRUITING)
• Cairo University, faculty of medicine — Cairo, Egypt (RECRUITING)
• Faculty of medicine, Ain Shams University — Cairo, Egypt (RECRUITING)
• Faculty of medicine, Azhar University — Cairo, Egypt (RECRUITING)
• Faculty of medicine, october 6 Univeristy — Cairo, Egypt (RECRUITING)
• Faculty of medicine, Luxor university — Luxor, Egypt (RECRUITING)
• faculty of medicine, Minya University — Minya, Egypt (RECRUITING)
• Faculty of medicine, Tanta University — Tanta, Egypt (RECRUITING)

Study contacts

• Study coordinator: Ahmed A Shokeir+2, professor of Urology

Conditions: Erectile Dysfunctions, Erectile Dysfunction, ED, Sildenafil, Tadalafil, PDE5i Non-Responders, Combination Therapy