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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| indomethacin treatment group | Experimental | indomethacin (75mg, bid) + omeprazole (20mg, qd) |
|
| placebo treatment group | Placebo Comparator | placebo (75mg, bid) + omeprazole (20mg, qd) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| indomethacin | Drug | indomethacin (75mg, bid, po, 14days) |
|
| 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 |
| 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) |
| 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 |
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:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital Of Guangzhou Medical University | Recruiting | Guangzhou | Guangdong | 520120 | China |
Study Protocol Statistical Analysis Plan (SAP)
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| ID | Term |
|---|---|
| D000096822 | Chronic Cough |
| ID | Term |
|---|---|
| D003371 | Cough |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D012818 | Signs and Symptoms, Respiratory |
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| ID | Term |
|---|---|
| D007213 | Indomethacin |
| D009853 | Omeprazole |
| ID | Term |
|---|---|
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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a randomized, double-blind, placebo-controlled trial
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| Placebo | Drug | placebo (75mg, bid, po, 14days) |
|
| Omeprazole | Drug | placebo (20mg, qd, po, 14days) |
|
| 1, 7, 14 day |
| cough reflex sensitivity | Outcome measure: LogC5 of Capsaicin cough challenge | 1, 7, 14, 21 day |
| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D001562 | Benzimidazoles |