A Phase 4 interventional study of Morphine Sulphate and Morphine Sulphate + Cough Control Therapy in Cough, Refractory Chronic Cough and Unexplained Chronic Cough, sponsored by McMaster University. Not yet recruiting at 5 sites in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-19.
Sponsored by McMaster University · Phase 4, Interventional, and Treatment
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.
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 independent 1:1 randomization to pharmacotherapy-either low-dose morphine (up to 5 mg twice daily) or pregabalin (up to 150 mg twice daily)-and concurrent cough control therapy (CCT) or no CCT. 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.
142 studies on the registry are indexed under Chronic Cough; 39 are open to participants now.
This study's planned enrollment of 124 is above the median of 60 across 104 interventional studies indexed under Chronic Cough.
Browse Chronic Cough studies →McMaster University is the lead sponsor of 741 studies on the registry; 127 are open to participants now.
Of its 7 completed or terminated interventional studies of FDA-regulated products, 3 (43%) have results posted.
Compared within Chronic Cough, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Cough. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Females of who:
Females who are not of child-bearing potential will be defined as females who have undergone a sterilization procedure (e.g., hysterectomy, bilateral oophorectomy, bilateral tubal ligation, complete endometrial ablation) or have been for at least 1 year prior to screening.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
FEV1
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Oral morphine sulphate given up to 5 mg twice daily.
Drug: Morphine Sulphate
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).
Combination Product: Morphine Sulphate + Cough Control Therapy
Oral pregabalin given up to a maximum tolerated dose of 150 mg twice daily.
Drug: Pregabalin
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).
Combination Product: Pregabalin + Cough Control Therapy
Oral morphine sulphate given up to 5 mg twice daily.
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).
Oral pregabalin given up to a maximum tolerated dose of 150 mg twice daily.
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).
Change from baseline in 24-hour cough frequency (coughs/hour) measured by the VitaloJAK ambulatory cough monitor at 6 weeks
Time frame: 6 weeks
Change from baseline in awake cough frequency (coughs/hour) measured by the VitaloJAK ambulatory cough monitor at 6 weeks
Time frame: 6 weeks
Change from baseline in sleep cough frequency (coughs/hour) measured by the VitaloJAK ambulatory cough monitor at 6 weeks
Time frame: 6 weeks
Change from baseline in cough bouts (defined by inter-cough intervals) measured by the VitaloJAK ambulatory cough monitor at 6 weeks
Time frame: 6 weeks
Change from baseline in cough severity on the McMaster Cough Severity Questionnaire at 6 weeks
Time frame: 6 weeks
Change from baseline in cough severity on the 100-mm visual analogue scale at 6 weeks
Time frame: 6 weeks
Change from baseline in cough-specific quality of life on the Leicester Cough Questionnaire at 6 weeks
Time frame: 6 weeks
Proportion of patients achieving a ≥30% reduction in 24-hour cough frequency at 6 weeks
Time frame: 6 weeks
Proportion of patients achieving a ≥30-mm reduction on the 100-mm cough severity visual analogue scale at 6 weeks
Time frame: 6 weeks
Proportion of patients achieving a ≥1.3-point improvement on the Leicester Cough Questionnaire at 6 weeks
Time frame: 6 weeks
Change from week 6 (end of randomized phase) in cough severity on the McMaster Cough Severity Questionnaire at 6 and 12 months
Time frame: 6 and 12 months
Change from week 6 (end of randomized phase) in cough severity on the 100-mm visual analogue scale at 6 and 12 months
Time frame: 6 and 12 months
Change from week 6 (end of randomized phase) in cough-specific quality of life on the Leicester Cough Questionnaire at 6 and 12 months
Time frame: 6 and 12 months
Proportion of patients with any adverse event for each intervention at 6 weeks, 6 months, and 12 months
Time frame: 6 weeks, 6 months, and 12 months
Proportion of patients with treatment-related adverse events for each intervention at 6 weeks, 6 months, and 12 months
Time frame: 6 weeks, 6 months, and 12 months
Proportion of patients with serious adverse events for each intervention at 6 weeks, 6 months, and 12 months
Time frame: 6 weeks, 6 months, and 12 months
Proportion of patients with adverse events leading to treatment discontinuation for each intervention at 6 weeks, 6 months, and 12 months
Time frame: 6 weeks, 6 months, and 12 months
Plan to share: Yes — The Principal Investigator and Steering Committee will review requests for data sharing on an individual basis. After the main publication of the FORTITUDE trial, there may be opportunities to conduct additional analyses on the data collected. Formal requests for additional analyses with a submitted rationale and analysis plan will be made to the Principal Investigator and reviewed with the Steering Committee.
Start is estimated for Sep 2026; primary completion for Sep 2029, 35 months later.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Morphine · Pregabalin