Chronic cough treatment: the McGill experience
| ISRCTN | ISRCTN33222797 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN33222797 |
| Protocol serial number | CC2014 |
| Sponsor | McGill University Health Centre |
| Funder | The Department of Otolaryngology - Head & Neck Surgery, McGill University Health Centre (Canada) |
- Submission date
- 26/11/2014
- Registration date
- 06/01/2015
- Last edited
- 29/10/2019
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Signs and Symptoms
Plain English summary of protocol
Background and study aims
Having a chronic cough can strongly impact the quality of life of patients. One possible cause is post-viral vagal neuropathy, whereby a nerve (the vagus nerve) that provides sensation to the larynx (or voicebox) and triggers the cough reflex is damaged by a virus. This makes the nerve hyper-sensitive. The patient will react more than other people to irritants, such as allergens, smoke, cold air and perfumes, all of which trigger the cough reflex. This leads to a unrelenting chronic cough that does not seem to get better with time and can go in for many months, or even years. At the moment, the treatment we give to our patients is amitriptyline (Elavil©). We have noticed a great improvement of chronic cough in our patients when treated with this medication. Amitriptyline has been used for several years for the treatment of neuropathic pain (pain caused by damaged nerves). It is therefore thought to work in the same way in treating postviral vagal neuropathy leading to chronic cough. Another medication, gabapentin (Neurontin©) is also reported as a successful treatment for chronic cough. Just like amitriptyline, it has neuromodulator effects, which are used very commonly for neuropathic pain. Here, we want to look at two drugs, both of which have been proven to help with chronic cough and find out which one acts more quickly and has fewer side effects.
Who can participate?
Adults who have had cough symptoms for at least 3 months.
What does the study involve?
Patients are randomly allocated into one of two groups. Those in group 1 are given amitriptyline. Those in group 2 are given gabapentin. To understand if patients are showing responses to the medication, phone interviews are conducted 10 days and then 21 days after the treatment starts. For each of these two visits, each participant completes a questionnaire asking them about their chronic cough and are asked if they are experiencing side effects. 6 weeks after the treatment has started, patients are seen in clinic by a laryngologist. The questionnaire is filled in again and questions asked about side effects. The patient also undergoes a direct laryngoscopy to see how swollen (inflamed) their vocal cords are. The reflux finding score (a way of measuring the laryngopharyngeal reflux) is also completed.
What are the possible benefits and risks of participating?
Both amytriptyline and gabapentin have been shown to improve chronic cough. They have also both been used for many years in the treatment of other conditions, such as various neuropathies. Both are extremely safe drugs, with few side effects. The most common side effects of amitriptyline are dry mouth and dizziness. With gabapentin, the most common side effect is low energy and muscle aches.
Where is the study run from?
1. Montreal General Hospital (Canada)
2. Royal Victoria Hospital, Montreal (Canada)
When is the study starting and how long is it expected to run for?
June 2013 to June 2016
Who is funding the study?
The Department of Otolaryngology - Head & Neck Surgery, McGill University Health Centre (Canada)
Who is the main contact?
Ms Emily Kay-Rivest
emily.kay-rivest@mail.mcgill.ca
Contact information
Public
1199 Bishop St. apt 207
Montreal
H3G0A7
Canada
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomized controlled, non-inferiority trial. |
| Secondary study design | Randomised controlled trial |
| Scientific title | The McGill experience with Chronic Cough Treatment: A Phase 2 Pilot Study |
| Study objectives | Although both amitryptiline and gabapentin have been proven to improve chronic cough caused by post-viral neuropathy, we hypothesize that one agent has a more rapid onset of action and a better side effect profile. |
| Ethics approval(s) | 1. MUHC Ethics Committee, 26/06/2014, ref. 13-064 BMD 2. Health Canada, 15/01/2014, ref. 170996 |
| Health condition(s) or problem(s) studied | Chronic cough secondary to irritable larynx and post-viral neuropathy |
| Intervention | Recruitment of patients (N=100) from our regular clinical activities, on 3 different sites: Montreal General hospital, Royal Victoria hospital, Jewish General hospital. Patients who meet the inclusion criteria will be randomized to treatment with either amitriptyline or gabapentin. 1. Gabapentin: Day 1: 150 mg QHS Day 2: 300 mg QHS Day 3: 300 mg BID We will conduct a phone interview after 10 days of treatment to assess for improvement and if there is none, we will increase to 300 mg TID. We will do another phone interview 3 weeks after initiation of treatment. We will also see the patient after 2 months of treatment commencement. 2. Amytriptyline Starts at 10 mg qHS, followed by increases of 10 mg every 3 weeks depending on symptomatic relief, with a maximum of 50 mg qHS. |
| Intervention type | Drug |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | 1. Amitriptyline 2. Gabapentin |
| Primary outcome measure(s) |
To observe the quality of life and symptomatic outcomes of chronic cough patients when treated with amitriptyline (Elavil) vs. gabapentin (Neurontin) therapy as measured by the Leicester cough questionnaire at 10 days, 3 weeks, 6 weeks and 4 months after initiation of treatment. |
| Key secondary outcome measure(s) |
1. To evaluate the side effect profile of this medication when used to treat chronic cough |
| Completion date | 01/06/2016 |
| Reason abandoned (if study stopped) | Cancelled |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | All |
| Target sample size at registration | 100 |
| Key inclusion criteria | Included patients will be patients having had cough symptoms for at least 3 months (chronic cough), and that have already been worked up by respirologists to rule out other etiologies of cough. These patients will have failed all other medical therapies: inhaled corticosteroids and single dose of antireflux medication. |
| Key exclusion criteria | 1. Patients without cough symptoms for over 3 months 2. Patients that have not been worked up by a respirologist and who have not attempted inhaled corticosteroids or antireflux medication 3. Patients who have been taking over the counter (OTC) antitussives, or angiotensin converting enzymes inhibitors medication 4. Patients who have been taking antibiotics in the last month for a respiratory tract infection 5. Patients who are smokers (both smoking and recent respiratory tract infection could confound our results) 6. Patients who are pregnant or breast feeding 7. Patients with abnormal hepatic or kidney function tests (creatinine over 100, ALT over 36 U/L, AST over 35 U/L, total bilirubin over 26 mmol/L) 8. Patients with abnormalities on the electrocardiogram that have not been cleared by a cardiologist 9. Patients with significant cardiac, renal, hepatic, epileptic, hematologic antecedents 10. Patients taking anticholinergic or sympathomimetic medications 11. Patients above the age of 70 |
| Date of first enrolment | 01/12/2014 |
| Date of final enrolment | 01/12/2014 |
Locations
Countries of recruitment
- Canada
Study participating centres
Montreal
H3G 1A4
Canada
Montreal
H4A 3J1
Canada
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan |
Editorial Notes
29/10/2019: The study was stopped due to it being cancelled.
27/10/2015: The scientific title has been changed from "Amitriptyline versus gabapentin in the treatment of chronic cough secondary to irritable larynx and post-viral neuropathy" to "The McGill experience with Chronic Cough Treatment: A Phase 2 Pilot Study".
