Fractional Concentration of Exhaled NO(FeNO) to Direct The Treatment of Sub-acute Cough

Coughing Clinical Trial

Official title:

Fractional Concentration of Exhaled NO(FeNO) to Direct The Treatment of Sub-acute Cough：A Prospective, Open Label, Randomized and Placebo-Controlled Trial

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT02655562
• Other study ID #: Beijing Chao Yang Hospital
• Status: Suspended
• Phase: Phase 4
• Start date: April 2016
• Est. completion date: February 2026

Study information

• Verified date: July 2022
• Source: Beijing Chao Yang Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cough is a common symptom that leads patients worldwide to seek medical attention. Subacute cough refers to a cough of 3-8-week duration, and is typically refractory to standard anti-tussive therapy, and a tendency to spontaneous healing was common. Few clinical trials have evaluated therapeutic options for subacute cough. Airway inflammation is an important feature of most of subacute cough, Cysteinyl leukotrienes and FeNO correlates with airway inflammation. Subacute cough often represents a prolonged post-viral response. Cysteinyl leukotrienes increase in virus infection. Airway inflammation induce epithelial cells produce iNOS(inducible nitric oxide synthase,iNOS), and FeNO increase in theory. Montelukast is a cysteinyl leukotriene type 1 receptor antagonist that is reported to improve cough16 and reduces FENO and prevents increases in FENO during reduction of inhaled corticosteroid dose, But A meta-analysis of the effectiveness of LTRA( leukotriene receptor antagonist,LTRA)in treating children with prolonged non-specific cough concluded that, with the lack of evidence, the routine use of LTRA in treating children with non-specific cough cannot be recommended. A randomised, placebo-controlled trial showed montelukast is not an effective treatment for postinfectious cough. Non-specialists or general practitioners of Japan prescribe LTRA very often, which increase. The aim is to research whether FeNO can be used as a biomarker to direct montelukast treatment and optimize treatment regimen of sub-acute cough.

Description:

This project is a prospective, open label, randomized and controlled trial. All subacute cough patients that met the inclusion/exclusion criteria were recruited after signing the consent form. Patients were randomized into biomarker treatment armand standard treatment arm. Patients in biomarker treatment arm and FENO≥25ppb were given Montelukast Sodium Tablets (p.o., 10mg, q.d.) . Patients in biomarker reatment arm and FENO<25ppb were given placebo (p.o., 10mg, qd). Patients in standard treatment arm and FENO≥25ppb were given placebo (p.o., 10mg, qd). Patients in standard treatment arm and FENO<25ppb were given Montelukast Sodium Tablets (p.o., 10mg, q.d.) .All treatment regimens lasted for 10 days and no other antitussive/decongestant or bronchodilators are given to any patients. Examine results of all patients from all arms were recorded before and after the 10 day treatment. The examine recorded are FENO levels, cough symptom assessment, cough visual assessment, Leicester cough questionnaire, total white blood cell count, neutrophil blood percentage, eosinophil blood percentage. Patient cough free days after treatment and Montelukast Sodium Tablets . Follow up was carried out at the 8th week after first record of symptom and 2 month after treatment.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 200
• Est. completion date: February 2026
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Cough is the main or only clinical symptom and was persistent for 3-8 weeks Chest X-ray reveals no noticeable pathological changes
• more than 18 year old, regardless of gender and ethical background
• Not taking angiotensin-converting enzyme inhibitor
• Patients must join the programme voluntarily and are able to attend examination and follow-up sessions

Exclusion Criteria:

• Patients diagnosed with allergic rhinitis, chronic nasosinusitis or bacterial respiratory tract infections
• Patients diagnosed with severe reportorial disease of other severe systemic disease
• Patients who are allergic to any drugs to be tested
• Patients who are non-cooperative during examination sessions or other steps of the trial
• Patients who are not able to or refuse to sign consent

Related Conditions & MeSH terms

• Cough
• Coughing

Intervention

Drug:
• Montelukast
Patients in biomarker treatment arm and FENO=25ppb were given Montelukast Sodium Tablets (p.o., 10mg, qd) . Patients in biomarker reatment arm and FENO<25ppb were given placebo (p.o., 10mg, qd). Patients in standard treatment arm and FENO=25ppb were given placebo (p.o., 10mg, qd). Patients in standard treatment arm and FENO<25ppb were given Montelukast Sodium Tablets (p.o., 10mg, q.d.).All treatment regimens lasted for 10 days and no other antitussive/decongestant or bronchodilators are given to any patients.

Locations

Country	Name	City	State
China	Mingming Jiang	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Chao Yang Hospital

Country where clinical trial is conducted

China, 

References & Publications (18)

Birring SS, Prudon B, Carr AJ, Singh SJ, Morgan MD, Pavord ID. Development of a symptom specific health status measure for patients with chronic cough: Leicester Cough Questionnaire (LCQ). Thorax. 2003 Apr;58(4):339-43. — View Citation

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Gentile DA, Fireman P, Skoner DP. Elevations of local leukotriene C4 levels during viral upper respiratory tract infections. Ann Allergy Asthma Immunol. 2003 Sep;91(3):270-4. — View Citation

Grant CC. Postinfectious cough and pertussis in primary care. Lancet Respir Med. 2014 Jan;2(1):2-3. doi: 10.1016/S2213-2600(13)70260-1. Epub 2013 Dec 2. — View Citation

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Kwon NH, Oh MJ, Min TH, Lee BJ, Choi DC. Causes and clinical features of subacute cough. Chest. 2006 May;129(5):1142-7. — View Citation

Lim KG, Mottram C. The use of fraction of exhaled nitric oxide in pulmonary practice. Chest. 2008 May;133(5):1232-42. doi: 10.1378/chest.07-1712. Review. — View Citation

Mincheva RK, Kralimarkova TZ, Rasheva M, Dimitrov Z, Nedeva D, Staevska M, Papochieva V, Perenovska P, Bacheva K, Dimitrov VD, Popov TA. A real - life observational pilot study to evaluate the effects of two-week treatment with montelukast in patients with chronic cough. Cough. 2014 Mar 20;10(1):2. doi: 10.1186/1745-9974-10-2. — View Citation

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Sandrini A, Ferreira IM, Gutierrez C, Jardim JR, Zamel N, Chapman KR. Effect of montelukast on exhaled nitric oxide and nonvolatile markers of inflammation in mild asthma. Chest. 2003 Oct;124(4):1334-40. — View Citation

Sato S, Saito J, Sato Y, Ishii T, Xintao W, Tanino Y, Ishida T, Munakata M. Clinical usefulness of fractional exhaled nitric oxide for diagnosing prolonged cough. Respir Med. 2008 Oct;102(10):1452-9. doi: 10.1016/j.rmed.2008.04.018. Epub 2008 Jul 9. — View Citation

Spector SL, Tan RA. Effectiveness of montelukast in the treatment of cough variant asthma. Ann Allergy Asthma Immunol. 2004 Sep;93(3):232-6. — View Citation

Tamaoki J, Kondo M, Sakai N, Nakata J, Takemura H, Nagai A, Takizawa T, Konno K. Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. The Tokyo Joshi-Idai Asthma Research Group. Am J Respir Crit Care — View Citation

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van Schaik SM, Tristram DA, Nagpal IS, Hintz KM, Welliver RC 2nd, Welliver RC. Increased production of IFN-gamma and cysteinyl leukotrienes in virus-induced wheezing. J Allergy Clin Immunol. 1999 Apr;103(4):630-6. — View Citation

Wang K, Birring SS, Taylor K, Fry NK, Hay AD, Moore M, Jin J, Perera R, Farmer A, Little P, Harrison TG, Mant D, Harnden A. Montelukast for postinfectious cough in adults: a double-blind randomised placebo-controlled trial. Lancet Respir Med. 2014 Jan;2(1):35-43. doi: 10.1016/S2213-2600(13)70245-5. Epub 2013 Dec 2. — View Citation

Wedde-Beer K, Hu C, Rodriguez MM, Piedimonte G. Leukotrienes mediate neurogenic inflammation in lungs of young rats infected with respiratory syncytial virus. Am J Physiol Lung Cell Mol Physiol. 2002 May;282(5):L1143-50. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Leicester cough questionnaire	Change in Leicester Cough Questionnaire(LCQ) total and domain scores at 10 days post randomisation	10 days
Secondary	cough visual assessment	Change in Leicester Cough Questionnaire(LCQ) physical,psychological and social domain scores at 10 days post randomisation	10 days