Effects of the Addition of Nedocromil Sodium to Maintenance Bronchodilator rherapy in the Management of Chronic Asthma (Part 3)Trial Design

A double-blind, parallel group design was used. Following a two-week baseline, patients were randomly allocated, using a coding sheet, to receive either nedocromil sodium 4 mg twice daily or a matching placebo. Both test treatments were given via pressurized metered dose inhalers. To qualify for the test treatment phase, patients had to have recorded a minimum total symptom score of 14 (see “Efficacy Variables” section) over seven consecutive baseline days. Theophylline therapy was continued at the pretrial dose during the baseline and during the first four weeks of the test treatment period. At the end of week 4, the dose of theophylline was reduced by either one half (12 nedocromil sodium; nine placebo) or one third (six nedocromil sodium; eight placebo) in those patients taking one or two, or 1.5 tablets, respectively. purchase birth control pills

After six weeks of test treatment use, theophylline therapy was stopped. Use of inhaled {J2-bronchodilators as necessary was permitted throughout the trial period. Patient admission ran from February 25, 1987 to September 15, 1987 and final clinic visits ran from May 6, 1987 to November 24, 1987. In five instances, one nedocromil sodium-treated patient and one placebo-treated patient had the same day for their clinic visits. The design and arrangement of visits made it highly unlikely that unblinding of the study would occur. The prot(x*ol was approved by the hospital ethical committee and the National Drugs Advisory Board.Fitient Characteristics

The patient characteristics are summarized in Table 1. The treatment groups were well matched, with no significant differences (p>0.05) between the groups for any admission variable.

Efficacy Variables

On admission and at clinic visits at the end of the baseline and weeks 4, 5, 6, and 8 of the treatment period, the clinician assessed the severity of asthma using a five-point scale (0 = no symptoms to 4 = very severe) and recorded lung (unction values for peak expiratory flow (PEF), FEV,, and forced vital capacity (FVC).

During the baseline and throughout the treatment period, the patients completed daily diary cards recording the following: nighttime asthma, morning tightness, daytime asthma, and cough severity’ using five-point scales (0 = none to 4 = very severe); morning and evening PEF values (best of three measurements); day and nighttime use of inhaled P2-bronchodilators; and use of theophyllines and test treatment.

At the end of week 4 and week 8, both patient and clinician expressed their opinion of the overall efficacy of treatment, using a five-point scale (l = very effective to 5 = made condition worse). The clinician also commented on the success in terms of symptoms of the reduction (week 6) and the withdrawal (week 8) of theophylline therapy.

Table I—Patient Characteristics at Baseline

NedocromilSodium Placebo
No. of patients, M/F 18 (12/6) 17 (11/6)
Mean age, yr (Range) Type of asthma 27.2 28.2
Extrinsic 16 16
Mixed Severity in past 12 mo 2 1
Mild 9 13
Moderate 8 3
Severe 1 0
No record 0 1
Mean duration of asthma, yr (Range) 9.7 11.7
Mean FEV,, L (Range) 2.35(1.41-4.36) 2.57(1.39-3.57)
% reversibility FEV,, Mean (Range) Daily dose of theophylline, mg 34.4 (20.2-69.3) 28.1 (17.6-52.9)
400 8 5
500 0 1
600 6 8
700 1 0
800 3 3
Mean daily dose of theophylline, mg 550 570


Category: asthma / Tags: Bronchodilator therapy, Chronic Asthma, Nedocromil Sodium