Indomethacin for Refractory Chronic Cough

Study Overview
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Brief Summary
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Chronic cough is a common complain of patients in respiratory clinic and its global prevalence was up to 9.6%. Persistent cough of unexplained origin is a significant health issue that occurs in up to 5% to 10% of patients seeking medical assistance for a chronic cough and from 0% to 46% of patients referred to specialty cough clinics. Previous studies showed that sputum prostaglandin D2( PGD2) and prostaglandin E2 (PGE2) concentrations were significantly higher in chronic cough. And some research showed that Inhaled PGE2 /PGF2α /PGD2 / PGI2/ 6-oxo-PGF1a could induced cough. And PGE2 /PGF2α/PGI2/thromboxane A2 (TXA2) also increased the sensitivity of the cough reflex. All these five primary prostaglandins were synthesized though the metabolism of arachidonic acid via the cyclooxygenase pathway. Indomethacin is a strong inhibitor of cyclooxygenase , which decrease the level of prostaglandins in airway. The investigator's preliminary study showed that indomethacin could relieve cough and improve cough sensitivity of some patients with refractory cough. Therefore this randomized, double-blind, placebo-controlled trial were designed to investigate whether indomethacin can relive cough in patients with refractory cough and to explore the possible mechanism of indomethacin in improving cough in patients with refractory cough.

Official Title
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Indomethacin for Refractory Chronic Cough: a Randomized, Double-blind, Placebo-controlled Trial

Conditions
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Refractory Chronic Cough

Intervention / Treatment
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* Drug: indomethacin
* Drug: Placebo
* Drug: Omeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1）18 years old ≤ age ≤ 60 years old, male or female; 2）Chronic cough lasting more than 8 weeks as the sole or predominant symptom, without abnormalities on chest radiograph; 3）Chronic cough remains after investigation and supervised therapeutic trial(s) conducted according to Clinical Practice Guidelines for Diagnosis and Management of Cough (2015) 4）Cough VAS (0-100mm) ≥ 30 mm Exclusion Criteria: Patients had any contraindications to indomethacin; Patients had active respiratory disease (such as chronic obstructive pulmonary Disease or untreated asthma), or moderate or above obstructive or restrictive or mixed pulmonary ventilation dysfunction; Patients had a respiratory tract infection in the month before randomization; Patients were taking an angiotensin-converting enzyme inhibitor; Patient were pregnant or breastfeeding, or had impaired kidney function; Current and recent smokers (<6 months' abstinence), or ex-smokers with more than 20 pack-years (20 cigarettes per pack).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: a randomized, double-blind, placebo-controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: indomethacin treatment group<br>indomethacin (75mg, bid) + omeprazole (20mg, qd) | Drug: indomethacin<br>* indomethacin (75mg, bid, po, 14days)<br>* Other names: Indometacin sustained-release capsules;Drug: Omeprazole<br>* placebo (20mg, qd, po, 14days)<br>|
| Placebo Comparator: placebo treatment group<br>placebo (75mg, bid) + omeprazole (20mg, qd) | Drug: Placebo<br>* placebo (75mg, bid, po, 14days)<br>Drug: Omeprazole<br>* placebo (20mg, qd, po, 14days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline Cough Severity | Outcome measure: Cough visual analogue scales (Cough VAS). Score range: 0-100mm (0 mean no cough, 100 represent that cough is the most severe in his/her life. Scoring higher on cough VAS mean more severe cough he/she has. ) | 1, 3, 7, 10, 14, 21day | 
| Change of cough-specific-quality-of-life | Outcome measure: Leicester Cough Questionnaire (LCQ). Score range: 3-21 (Higher values represent a better outcome.) | 1, 14, 21 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| frequency of patients'coughs | Outcome measure: cough count in one hour | 1, 7, 14 day | 
| laryngeal dysfunction score | Outcome measure: Laryngeal dysfunction questionnaire (Higher score represent a better outcome) | 1, 7, 14 day | 
| cough reflex sensitivity | Outcome measure: LogC5 of Capsaicin cough challenge | 1, 7, 14, 21 day |