Journal Reporting

Dr. Pravinkumar A. WahaneJR II, Dept. Of Pharmacology

B.J.G.M.C. Pune

A randomized, double-blind, placebo controlled trial of oral montelukast in acute asthma exacerbation

Ali Bin S Z, Nawal S, Ali K, Safia A et al.

BMC Pulmonary Medicine 2013, 13:20, 1-7

Introduction

Asthma associated with chronic airway inflammation with recruitment of a number of inflammatory cells including T-cells, mast cells and eosinophils

Ranked as major contributor to emergency department visits

Incidence is on rise all across world, especially in paediatric population, with bronchial asthma accounting for 4% of the paediatric out-patient visits

Introduction

Interaction of these mediators with the Type 1 cysteinyl leukotriene receptors (CysLT-1), located on inflammatory cells and structural cells of airways implicated in :

Inflammatory cell infiltration,

Initiation of bronchial smooth muscle contraction,

Mucus secretion and

Increased vascular permeability

Ultimately leads to airway narrowing Montelukast is M.C. used (CysLT-1) antagonist

Introduction

Shown to improve symptoms & lung function (FEV1) within 15 minutes of administration in chronic asthma with its effects lasting for a period of at least 24 hours

Existing therapeutic modalities for acute asthma include oxygen and short acting β2 agonist bronchodilators in order to promptly reverse airflow obstruction

Hypothesis Treatment with a leukotriene receptor antagonist (LTRA),

montelukast sodium would improve airway obstruction and clinical outcomes in acute asthma exacerbation and would subsequently decrease the duration of hospital stay

Materials and Methods

Randomized, double-blind, placebo controlled parallel group drug trial conducted over a period of two years from February 2006 to February 2008 in Tertiary care hospital

Patients presenting to the emergency department with acute asthma exacerbation were included in study after primary screening

Ethics Review Committee approval was Obtained

Informed Consent obtained from subjects before inclusion in the study

Materials and Methods

Inclusion Criteria Diagnosis of acute asthma exacerbation that required

hospitalization as defined by the Global Initiative for Asthma (GINA) Guidelines Pts. with FEV1 < 70% predicted aged 16 yrs or more Pts. with PEF < 300 L/min aged 16 yrs or more

After receiving 30 minutes of initial treatment in the ER Respiratory rate > 24 breaths/min No improvement in symptoms such as shortness of breath

or wheezing

Materials and Methods

Exclusion Criteria Age <15 years , Pregnancy FEV1 > 70% predicted OR PEF > 300 L/min History of tobacco use of >10 years Concomitant therapy with systemic Corticosteroids or

leukotriene modifiers at any time in the past 4 weeks at the time of admission

Any concurrent acute medical condition like AMI, CCF, DKA or Shock

Acute respiratory failure requiring mechanical ventilation

Study Procedure

Patients were assigned to Treatment group (Montelukast) and Placebo group randomly by computer generated randomization sequence

Patients in Group 1 (Treatment Group) : -

Received standard therapy & oral montelukast sodium (10 mg once daily)

Patients in Group 2 (Placebo Group) :-

Received standard therapy along with a placebo

Study Design

Outcome Assessment

Primary Outcomes Improvement in lung function measured as PEF and

FEV1 over the course of hospital stay and discharge Duration of hospital stay

Secondary Outcomes Development of complications such as :

Respiratory failure, Cardiac arrest and/or Death

Statistical Analysis

Categorical variables were analyzed using Chi-square test

Continuous variables were analyzed using Fisher exact

All analyses were conducted by using the Statistical package for social science (SPSS Release 15.0)

p-values were considered as statistically significant if < 0.05

Results : Baseline Characteristics

Results : Baseline Characteristics

RESULTS

Primary outcome measures

No significant difference in the PEF between both treatment groups during the hospital stay and at discharge

No Statistically significant difference in Mean PEF of Montelukast and Placebo groups at time of discharge

No Statistically significant difference in Mean FEV1 in Montelukast and Placebo groups at time of discharge

Mean duration of Hospital stay for patients belonging to montelukast and placebo groups was 3.67 ± 1.86 days and 3.72 ± 2.02 days respectively (p – 0.90)

Primary outcome measures

Primary outcome measures

Secondary outcome measures Two patients, one from each arm, developed respiratory

failure

No patient in either group was withdrawn due to worsening asthma or adverse drug effect from the study

Discussion

Study did not reveal significant differences in : PFTs measured as FEV1 at admission and discharge &

PEF measured at specific intervals Length of hospital stay in patients hospitalized with

acute asthma exacerbation that were given oral montelukast vs. placebo

Efficacy and tolerability profile of oral montelukast were comparable to placebo and no serious adverse effects were encountered

Study findings were not consistent with Ramsay et al, Silverman et al, Camarago et. al. & Adaichi et. al.

Conclusion

Study suggests that there is no added benefit of using montelukast along with the standard therapy for the management of acute asthma exacerbation in hospitalized adult population

Larger scale multicentre trials needed to better evaluate the role of cysteinyl leukotriene's antagonists in treating acute exacerbations of asthma

Comments

Clinical Trial Registration No. - Mentioned Title – Gives clear idea about aim and study design but not

about the dosing pattern / route of administration of Montelukast

Introduction – Background information and purpose of study mentioned

Materials and Methods – Ethical Approval and informed consent has been obtained

Place ,Duration of study and Study design mentioned Randomization method & inclusion / Exclusion criteria

mentioned

Comments

Source of Drug – Mentioned

Results – Statistical Test applied mentioned, Statistical software used for analysis mentioned, appropriate tables and figures included

Discussion – Results repeated, Relevant studies mentioned, Limitations of the study mentioned

Results - Emphasizes need for further studies regarding Montelukast use in acute exacerbation of asthma

Supports and Conflict of Interest - Mentioned as Nil