Clinical trial NCT03738917: Effectiveness of Antitussives, Anticholinergics and Honey Versus Usual Care in Adults With Acute Bronchitis.
Official title: Effectiveness of Antitussives, Anticholinergics and Honey Versus Usual Care in Adults With Uncomplicated Acute Bronchitis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Bronchitis
Keywords: Cough; Dextromethorphan; Ipratropium; Honey.
Lead sponsor: Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina
Sponsor class: OTHER
Collaborators: name: Spanish Clinical Research Network - SCReN
First posted: 2018-11-13
Enrollment: 668
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentre, pragmatic, parallel group, open randomized trial.
Primary purpose: TREATMENT

Brief summary: This study, which is aimed at comparing the effectiveness of 3 symptomatic therapies (dextromethorphan, ipratropium and honey) associated with usual care and the usual care in adults with acute bronchitis, is a multicentre, pragmatic, parallel group, open randomised trial. Patients aged 18 or over with uncomplicated acute bronchitis, with cough \<3 weeks as the main symptom, scoring ≥ 4 in either daytime or nocturnal cough on a 7-point Likert scale, will be randomised to one of the 4 groups. Sample: 668 patients. The primary outcome will be the number of days with moderate-severe cough.

Detailed description: Despite the frequent use of therapies in acute bronchitis, encouraged by the over-the-counter availability in pharmacies, the evidence of their benefit is scarce, since only a few clinical trials have been published, with low sample sizes, poor methodological quality and mainly in children. The objective of this study is to compare the effectiveness of 3 symptomatic therapies (dextromethorphan, ipratropium and honey) associated with usual care and the usual care in adults with acute bronchitis. This will be a multicentre, pragmatic, parallel group, open randomised trial. Patients aged 18 or over with uncomplicated acute bronchitis, with cough for less than three weeks as the main symptom, scoring ≥ 4 in either daytime or nocturnal cough on a 7-point Likert scale, will be randomised to one of the following four groups: usual care, usual care + dextromethorphan 30 mg t.i.d., usual care + ipratropium bromide inhaler 20 µg 2 puffs t.i.d, or usual care + 30 mg (a spoonful) of honey t.i.d., all taken for up to 14 days. The exclusion criteria will be: pneumonia, criteria for hospital admission, pregnancy or lactation, concomitant pulmonary disease, associated significant comorbidity, allergy, intolerance or contraindication to any of the study drugs, admitted to a long-term residence, or inability to give informed consent. Sample: 668 patients. The primary outcome will be the number of days with moderate-severe cough in the intention-to-treat (ITT) population, i.e., the number of days from the randomisation visit until the last day the patient scores three or more in either daytime or nocturnal cough in the symptom diary. All patients will be given a symptom diary to be self-administered while symptoms are present. A second visit will be scheduled at day 2-3 for assessing evolution, with two more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance and complications. Patients still with symptoms at day 29 will be called six weeks after the baseline visit.

Eligibility criteria: Inclusion Criteria:

* age 18 years or older, and
* symptoms of acute bronchitis with cough starting within 3 weeks before study inclusion, and
* patients who score ≥ 4 in either the daytime and/or nocturnal cough on a 7-point Likert scale, and
* patients who consent to participate.

Exclusion Criteria:

* suspected pneumonia; if the professional suspects pneumonia, a chest X-ray will be recommended and the patient will be randomized if this diagnosis is discarded; or
* criteria for hospital admission (impaired consciousness, respiratory rate \> 30 breaths/minute, pulse \> 125 beats/minute, systolic blood pressure \<90 mm Hg or diastolic blood pressure \<60 mm Hg, temperature \> 104°F or oxygen saturation \<92%)
* pregnancy or breast feeding
* baseline respiratory disease such as chronic obstructive pulmonary disease, asthma, tuberculosis or bronchiectasis
* associated significant comorbidity, such as moderate-severe heart failure, dementia, acute myocardial infarction/recent cerebral vascular accident (\< 3 months), severe liver failure, severe renal failure
* immunosuppression, such as chronic infection by HIV, transplanted, neutropenic, or patients receiving immunosuppressive treatment
* active neoplasm
* terminal illness
* history of intolerance or allergy to any of the study treatments
* patients in whom, in the opinion of the investigator, treatment with dextromethorphan, ipratropium bromide or honey is contraindicated
* patients living in long-term institutions
* difficulty in conducting scheduled follow-up visits

Primary outcomes:
measure: Duration of moderate-severe cough in days in the four arms.
timeFrame: Day 29.
Secondary outcomes:
measure: Duration of cough in days in the four arms.
timeFrame: Days 15 and 29. If the patient continues to score 2 or more at day 29 will be called at day 43.
measure: Duration of moderate-severe daytime cough in days in the four arms.
timeFrame: Days 15 and 29. If the patient continues to score 3 or more at day 29 will be called at day 43.
measure: Duration of moderate-severe nocturnal cough in days in the four arms.
timeFrame: Days 15 and 29. If the patient continues to score 3 or more at day 29 will be called at day 43.
measure: Duration of moderate-severe symptoms in days in the four arms.
timeFrame: Days 15 and 29. If the patient continues to score 3 or more at day 29 will be called at day 43.
measure: Duration of severe symptoms in days in the four arms.
timeFrame: Days 15 and 29.
measure: Duration of symptoms in days in the four arms.
timeFrame: Days 15 and 29. If the patient continues to score 2 or more at day 29 will be called at day 43.
measure: Duration of moderate-severe cough in days according to the basal degree of bronchial hyper-reactiveness in the four arms.
timeFrame: The peak-flow will be determined at day 1.
measure: Percentage of antibiotics and different symptomatic treatments used in the four arms.
timeFrame: Days 2-4, 15 and 29.
measure: Number of days of absence from work in the four arms.
timeFrame: Day 15.
measure: Patients re-attendance for symptoms related to the episode of acute bronchitis within the first 42 days.
timeFrame: Day 29 and phone call at day 43.
measure: Number of complications related to the episode of acute bronchitis within the first 28-42 days.
timeFrame: Day 29-43.
measure: Patient satisfaction in the four arms.
timeFrame: Day 15 or 29.
measure: Number of adverse events in the four arms.
timeFrame: Days 2-4, 15 and 29.
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Nova Lloreda Health Center
state: Catalonia
city: Badalona
country: Spain
facility: Martí i Julià Health Center
state: Catalonia
city: Balaguer
country: Spain
facility: Balaguer Health Center
state: Catalonia
city: Barcelona
country: Spain
facility: Via Roma Health Centre
state: Catalonia
city: Barcelona
country: Spain
facility: La Marina Health Center
state: Catalonia
city: Barcelona
country: Spain
facility: CAP Passeig Maragall (EAP Camp de l'Arpa)
state: Catalonia
city: Cornellà De Llobregat
country: Spain
facility: Cornellà - La Gavarra Health Center
state: Catalonia
city: Pineda De Mar
country: Spain
facility: Pineda de Mar Health Center
state: Catalonia
city: Sabadell
country: Spain
facility: Ca n'OriacHealth Center
state: Catalonia
city: Sant Boi De Llobregat
country: Spain
facility: Molí Nou Health Center
state: Catalonia
city: Santa Coloma De Gramenet
country: Spain
facility: Singuerlin Health Center
state: Catalonia
city: Tarragona
country: Spain
facility: CAP Jaume I
state: Catalonia
Study officials:
affiliation: Catalan Institute of Health
name: Ana Moragas, MD PhD
role: STUDY_CHAIR
References:
citation: Llor C, Moragas A, Ouchi D, Monfa R, Garcia-Sangenis A, Gomez-Lumbreras A, Pera H, Pujol J, Morros R. Effectiveness of antitussives, anticholinergics, and honey versus usual care in adults with uncomplicated acute bronchitis: a multiarm randomized clinical trial. Fam Pract. 2023 Mar 28;40(2):407-413. doi: 10.1093/fampra/cmac112.
citation: Cots JM, Moragas A, Garcia-Sangenis A, Morros R, Gomez-Lumbreras A, Ouchi D, Monfa R, Pera H, Pujol J, Bayona C, de la Poza-Abad M, Llor C. Effectiveness of antitussives, anticholinergics or honey versus usual care in adults with uncomplicated acute bronchitis: a study protocol of an open randomised clinical trial in primary care. BMJ Open. 2019 May 16;9(5):e028159. doi: 10.1136/bmjopen-2018-028159.