Refractory Chronic Cough
Conditions
Brief summary
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.
Interventions
DRUGindomethacin
indomethacin (75mg, bid, po, 14days)
DRUGPlacebo
placebo (75mg, bid, po, 14days)
DRUGOmeprazole
placebo (20mg, qd, po, 14days)
Sponsors
The First Affiliated Hospital of Guangzhou Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
a randomized, double-blind, placebo-controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline Cough Severity | 1, 3, 7, 10, 14, 21day | 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. ) |
| Change of cough-specific-quality-of-life | 1, 14, 21 day | Outcome measure: Leicester Cough Questionnaire (LCQ). Score range: 3-21 (Higher values represent a better outcome.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| frequency of patients'coughs | 1, 7, 14 day | Outcome measure: cough count in one hour |
| laryngeal dysfunction score | 1, 7, 14 day | Outcome measure: Laryngeal dysfunction questionnaire (Higher score represent a better outcome) |
| cough reflex sensitivity | 1, 7, 14, 21 day | Outcome measure: LogC5 of Capsaicin cough challenge |
Other
| Measure | Time frame | Description |
|---|---|---|
| change of airway arachidonic acid metabolism | 1, 7, 14, 21 day | Concentration of PGE2, PGF2α, PGD2, 6-Keto-PGF1α, TXB2, leukotriene B4(LTB4) and cys-LTs in induced sputum |
Countries
China
Outcome results
None listed