Efficacy of Two Doses of Duloxetine and Amitriptyline in Subjects With Refractory Chronic Cough (MACS-1)

Efficacy of Two Doses of Duloxetine and Amitriptyline in Subjects With Refractory Chronic Cough (MACS-1)

Brief Summary:
This research study is evaluating the effectiveness of escalating doses of Amitriptyline and Duloxetine in reducing cough frequency in patients with refractory chronic cough (RCC).

Detailed Description:
This is a randomized, double-blind, placebo-controlled, parallel-arm, dose escalation study of Duloxetine & Amitriptyline in subjects with refractory chronic cough. Subjects will be screened during a period of up to 2 week and will undergo screening/ baseline cough monitoring. A total of 50 subjects who meet entry criteria will be randomly assigned in a 1: 1: 1: 1: 1 ratio to one of five treatment arms using stratified randomization in blocks of 10. Each arm will have two successive 4-week treatment periods (Blinded Period 1 & 2). After this, patients will be unblinded and receive routine clinical care. During the unblinded (routine clinical care) follow up phase; subjects will be initially offered the option of continuing amitriptyline or duloxetine based on their initial randomization arm. Subjects could also choose an alternative chronic cough therapy (e.g. pregabalin, gabapentin, 1% tetracaine lollipop or nebulized lidocaine or combination therapy).

Subjects in treatment arm 5, who received placebo during the 8 weeks blinded period will have a discussion regarding all available cough therapies. Patients will be offered the flexibility of therapy options during the unblinded follow up as they would during routine clinical care. Participation in the unblinded follow-up period will be optional.


Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A total of 50 subjects who meet entry criteria will be randomly assigned in a 1: 1: 1: 1: 1 ratio to one of five treatment arms using stratified randomization in blocks of 10. Each arm will have two successive 4-week treatment periods (Blinded Period 1 & 2). After this, patients will be unblinded and receive routine clinical care. Participation in the unblinded portion of the study is optional.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
During the initial 8- week period, this will be a double-blind study. Both subjects and all study personnel (except for the research pharmacist) will be blind to the treatment assignment. Unblinding for both subjects and study investigators will occur at the end of the 8-week blinded treatment period.

The subjects and all personnel involved with the conduct and the interpretation of the study, including the Investigators and other study personnel (except the research pharmacist) will be blinded to the treatment codes. Randomization data will be kept strictly confidential by the study statistician, and accessible only to authorized persons until the time of unblinding.

Only in the case of an emergency, when knowledge of the investigational product is essential for the welfare of a subject, the principal investigator may unblind a subject's treatment assignment during the 8-week blinded treatment period.

Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Dose-escalation Study Evaluating the Efficacy of Two Doses of Duloxetine & Amitriptyline in Subjects With Refractory Chronic Cough
Actual Study Start Date: November 1, 2021
Estimated Primary Completion Date: December 2023
Estimated Study Completion Date: December 2023

Arm:
- Treatment Arm 1:
Blinded Period 1 (1st 4 weeks): 30mg of Duloxetine Blinded Period 2 (2nd 4 weeks): 30mg of Duloxetine & 30mg of Placebo Unblinded (routine clinical care) follow up period: (up to 52 weeks): Subjects will be offered routine clinical care management for their chronic cough

- Treatment Arm 2:
Blinded Period 1 (1st 4 weeks): 30mg of Duloxetine Blinded Period 2 (2nd 4 weeks): 60mg of Duloxetine (2 pills of 30mg each) Unblinded (routine clinical care) follow up period: (up to 52 weeks): Subjects will be offered routine clinical care management for their chronic cough

- Treatment Arm 3:
Blinded Period 1 (1st 4 weeks): 25mg of Amitriptyline Blinded Period 2 (2nd 4 weeks): 25mg of Amitriptyline + 25mg of Placebo Unblinded (routine clinical care) follow up period: (up to 52 weeks): Subjects will be offered routine clinical care management for their chronic cough

- Treatment Arm 4:
Blinded Period 1 (1st 4 weeks): 25mg of Amitriptyline Blinded Period 2 (2nd 4 weeks): 50mg of Amitriptyline (2 pills of 25mg each) Unblinded (routine clinical care) follow up period: (up to 52 weeks): Subjects will be offered routine clinical care management for their chronic cough

- Treatment Arm 5:
Blinded Period 1 (1st 4 weeks): 30mg of Placebo Blinded Period 2 (2nd 4 weeks): 60mg of Placebo (2 pills of 30mg each) Unblinded (routine clinical care) follow up period: (up to 52 weeks): Subjects will be offered routine clinical care management for their chronic cough

View full details