Not yet recruitingPHASE4INTERVENTIONAL

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

The FORTITUDE study is for adults in Canada who have a cough that has lasted a long time and hasn't gone away despite trying other treatments. This is often called 'refractory' or 'unexplained' chronic cough. The study aims to compare two different medicines, low-dose morphine and pregabalin, which are thought to help calm down the nerves involved in coughing. It also tests a special 'cough control therapy' that uses virtual sessions with experts. Researchers want to see if these treatments work well on their own, or if combining a medicine with the therapy is even better. They will also look at any side effects and how people feel over time. The goal is to find more effective ways to help people manage their persistent coughs.

At a glance

Status

Not yet recruiting

Phase

PHASE4

Sponsor

McMaster University

Enrolment target

124

Start

01 Apr 2026

Estimated completion

01 Jul 2029

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

What is this study about?

If you've had a cough for a long time that just won't go away, even after trying different medicines or treatments, you might have what doctors call 'refractory' or 'unexplained' chronic cough. This can be really frustrating and impact your daily life.

This study, called FORTITUDE, is looking into new ways to help people like you. It's comparing two medicines: low-dose morphine and pregabalin. These medicines are believed to work by calming down overactive nerves that might be causing your cough. The study is also testing a special 'cough control therapy' where you learn techniques to manage your cough from experts like physiotherapists and speech-language pathologists through online sessions. Researchers want to understand if these treatments, either alone or when combined, can make a real difference.

By taking part, you could help doctors discover more effective and safer ways to treat stubborn chronic coughs in the future. The study will look closely at how often you cough and how the treatments affect your well-being over time. This kind of research is really important for improving the lives of many people who struggle with persistent coughs.

Key takeaways

The study explores new treatments for coughs that won't go away.
It tests two medicines (low-dose morphine, pregabalin) and online cough therapy.
Participation lasts 6 weeks, with an optional follow-up for up to a year.
You'll either get a medicine, therapy, or a combination of both.
It aims to find better ways to help people with persistent coughs.

Who may be eligible?

This study is particularly looking for adults, aged 18 or older, who live in Canada and have had a cough for a long time that hasn't cleared up with standard treatments.

You might be suitable if you have a chronic cough that doctors have tried to treat for an underlying cause (like asthma or reflux) but it hasn't gone away. Or, if you have a chronic cough where doctors haven't found a clear reason after checking things like chest X-rays and lung function tests, you might also be a good fit.

However, there are reasons why you might not be able to join. For example, if you've already tried these specific medicines (morphine or pregabalin) or the cough control therapy in the past and they haven't worked well. Also, if you're currently taking similar medicines for other conditions, or if you smoke, or have certain other lung conditions, this study might not be right for you. The study team will review all your health details carefully to make sure it's safe and appropriate for you to take part.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Are you 18 years old or older?
Do you have a long-lasting cough that hasn't responded to usual treatments?
Are you not currently taking medicines like morphine, pregabalin, gabapentin, or amitriptyline?
Have you stopped smoking for at least 6 months (if you were a heavy smoker)?
Do you not have other serious lung conditions like lung cancer or severe emphysema?

Answer every question to see your result.

What does participation involve?

If you decide to join this study, it will last for 6 weeks, with an optional follow-up period stretching up to a year. You'll be randomly assigned to one of four groups, meaning you have an equal chance of receiving one of the following: low-dose morphine, pregabalin, low-dose morphine plus cough control therapy, or pregabalin plus cough control therapy.

If you're in a group receiving medicine, you'll take either low-dose morphine (up to 5mg twice a day) or pregabalin (up to 150mg twice a day, gradually increasing if needed and tolerated). If you're assigned to receive cough control therapy, you'll have five online sessions over the 6 weeks with a trained physiotherapist and speech-language pathologist. Throughout the study, you'll have regular checks, likely involving answering questions about your cough and how you’re feeling, to help researchers understand how the treatments are working. The main thing they'll be looking at is how much your cough frequency changes after 6 weeks.

Potential risks and benefits

Taking part in any study has potential benefits and risks. A potential benefit of this study is that you might find a new way to manage your chronic cough, potentially improving your quality of life. You'll also be helping to advance medical knowledge, which could benefit many others in the future. Potential risks might include side effects from the medicines, such as drowsiness or dizziness, though the doses are generally low. If you're in the group receiving cough control therapy, it may take time and effort to learn the new techniques. All side effects will be carefully monitored by the study team. Remember, your participation is completely voluntary, and you can withdraw from the study at any time and for any reason, without it affecting your usual medical care.

Locations (5)

Respiratory Clinical Trials Centre, University of Calgary
Verified postcode
Calgary, Canada
Respiratory Research Lab, McMaster University
Verified postcode
Hamilton, Canada
St Joseph's Health Care London
Verified postcode
London, Canada
Institut universitaire de cardiologie et de pneumologie de Quebec - University Laval
Verified postcode
Québec, Canada
Centre de recherche du Centre Hospitalier Universitaire de Sherbrooke
Verified postcode
Sherbrooke, Canada

Common questions

What is 'refractory' or 'unexplained' chronic cough?

It means you've had a cough for a very long time (usually over 8 weeks) that hasn't improved with regular treatments or where doctors can't find a clear cause.

Are the medicines safe?

The medicines being tested are generally given at low doses. The study team will carefully monitor you for any side effects and support you throughout.

What does 'cough control therapy' involve?

This is a special therapy delivered online by experts who teach you techniques to help manage and reduce your coughing.

How long will the study last for me?

The main treatment part of the study lasts for 6 weeks, but there is an optional longer follow-up period for up to a year.

Will I know which treatment I'm getting?

Yes, this is an 'open-label' study, which means both you and the study team will know which treatment you are receiving.

How to find out more

Imran Satia, MD PhD

satiai@mcmaster.ca 905-521-2100 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.