NCT07288528

A 2x2 Factorial, Randomized, Open-label Trial to Evaluate Neuromodulators and Cough Control Therapy in Patients With Refractory or Unexplained Chronic Cough

A 2x2 Factorial, Randomized, Open-label Trial to Evaluate Neuromodulators and Cough Control Therapy in Patients With Refractory or Unexplained Chronic Cough (FORTITUDE)

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 124 (estimated)
• Sponsor: McMaster University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The FORTITUDE trial will provide head-to-head evidence on the benefits and harms of two commonly prescribed neuromodulators (low-dose morphine and pregabalin), the effectiveness of a virtual cough control therapy, exploratory assessment of potential synergy in combining these interventions, and the long-term outcomes of these treatments in patients with refractory or unexplained chronic cough.

Detailed description

FORTITUDE (FactOrial Randomized TrIal To evalUate neuromoDulators and cough control thErapy) is a 6-week, 2x2 factorial, randomized, open-label trial with an extension observational phase up to 1 year. The trial will include Canadian hospital sites enrolling 124 patients. Patients ≥18 years old with either refractory or unexplained chronic cough will undergo 1:1:1:1 randomization to receive either low-dose morphine (up to 5 mg twice daily) or pregabalin (up to a maximum tolerated dose of 150 mg twice daily) with or without cough control therapy. The cough control therapy will consist of five virtual sessions delivered over 6 weeks by a trained physiotherapist and speech-language pathologist. Change from baseline in 24-hour cough frequency at 6 weeks represents the primary outcome.

Conditions

• Cough
• Refractory Chronic Cough
• Unexplained Chronic Cough
• Cough Hypersensitivity Syndrome
• Chronic Cough

Interventions

Type	Name	Description
DRUG	Morphine Sulphate	Oral morphine sulphate given up to 5 mg twice daily.
COMBINATION_PRODUCT	Morphine Sulphate + Cough Control Therapy	Oral morphine sulphate given up to 5 mg twice daily and cough control therapy (5 virtual sessions delivered over 6 weeks by a trained physiotherapist and speech-language pathologist).
DRUG	Pregabalin	Oral pregabalin given up to a maximum tolerated dose of 150 mg twice daily.
COMBINATION_PRODUCT	Pregabalin + Cough Control Therapy	Oral pregabalin given up to a maximum tolerated dose of 150 mg twice daily and cough control therapy (5 virtual sessions delivered over 6 weeks by a trained physiotherapist and speech-language pathologist).

Timeline

• Start date: 2026-04-01
• Primary completion: 2029-04-01
• Completion: 2029-07-01
• First posted: 2025-12-17
• Last updated: 2025-12-17

Locations

5 sites across 1 country: Canada