Indomethacin for Refractory Chronic Cough

The First Affiliated Hospital of Guangzhou Medical University84 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Refractory Chronic Cough

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

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: 1. Patients had any contraindications to indomethacin; 2. 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; 3. Patients had a respiratory tract infection in the month before randomization; 4. Patients were taking an angiotensin-converting enzyme inhibitor; 5. Patient were pregnant or breastfeeding, or had impaired kidney function; 6. Current and recent smokers (\<6 months' abstinence), or ex-smokers with more than 20 pack-years (20 cigarettes per pack).

Outcomes

Primary Outcomes

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. )

Time frame: 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.)

Time frame: 1, 14, 21 day

Secondary Outcomes

frequency of patients'coughs

Outcome measure: cough count in one hour

Time frame: 1, 7, 14 day

laryngeal dysfunction score

Outcome measure: Laryngeal dysfunction questionnaire (Higher score represent a better outcome)

Time frame: 1, 7, 14 day

cough reflex sensitivity

Outcome measure: LogC5 of Capsaicin cough challenge

Time frame: 1, 7, 14, 21 day