Indomethacin for Refractory Chronic Cough

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

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 Overview

• Status: Unknown
• Conditions: Refractory Chronic Cough
• Intervention / Treatment: Drug: indomethacin; Drug: Omeprazole; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 84
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 520120
      • Recruiting
      • The First Affiliated Hospital of Guangzhou Medical University
      • Contact: Kefang Lai, PHD; Phone Number: 020 83062893; Email: klai@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
change of airway arachidonic acid metabolism	Concentration of PGE2, PGF2α, PGD2, 6-Keto-PGF1α, TXB2, leukotriene B4(LTB4) and cys-LTs in induced sputum	1, 7, 14, 21 day

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Guangzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2018
• Primary Completion (Anticipated): August 15, 2020
• Study Completion (Anticipated): December 30, 2020

Study Registration Dates

• First Submitted: August 31, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (Actual): September 7, 2018

Study Record Updates

• Last Update Posted (Actual): November 26, 2018
• Last Update Submitted That Met QC Criteria: November 22, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Gout Suppressants; Tocolytic Agents; Indomethacin; Omeprazole
• Other Study ID Numbers: YDMX02V2.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Study Protocol Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No