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Prospective follow-up and pulmonary functions from a placebo-controlled randomized trial of ribavirin therapy in
W J Rodriguez1, J Arrobio, R Fink
1Department of Pediatrics, Children's National Medical Center and George Washington University, Washington, DC 20010-2970, USA. eayala@cnmc.org
Insights
Ribavirin treatment for infants with respiratory syncytial virus lower respiratory tract infection showed no adverse effects and suggested long-term benefits in pulmonary function compared to placebo.
Area of Science:
- Pediatric Pulmonology
- Infectious Diseases
- Clinical Trials
Background:
- Respiratory Syncytial Virus (RSV) is a common cause of lower respiratory tract infections (LRTI) in infants.
- Long-term pulmonary sequelae following RSV LRTI are a significant concern.
- The efficacy and safety of antiviral treatments like ribavirin for RSV LRTI require further investigation.
Purpose of the Study:
- To evaluate long-term differences in adverse effects and pulmonary function in infants treated with ribavirin versus a placebo for RSV LRTI.
- To assess the impact of ribavirin on reactive airway disease, wheezing, and pneumonia incidence.
- To determine the effect of ribavirin on pulmonary function test (PFT) results and airway hyperresponsiveness.
Main Methods:
- A randomized trial comparing ribavirin to placebo in infants (1-33 months) with RSV LRTI.
- Long-term follow-up included monitoring respiratory illness episodes, wheezing, and pneumonia.
- Pulmonary function tests (PFTs) and methacholine challenge tests were administered in later years.
Main Results:
- Infants treated with ribavirin showed a trend towards fewer episodes of reactive airway disease, wheezing, and pneumonia compared to the placebo group.
- A significantly higher proportion of ribavirin-treated patients had normal or mild PFT results (53%) compared to placebo (0%).
- Weighted severity scores indicated a long-term beneficial effect of ribavirin therapy, although statistical significance varied across analyses.
Conclusions:
- Ribavirin treatment for RSV LRTI in infants did not result in identified outward adverse effects.
- No increase in reactive airway disease, wheezing, or pneumonia was observed in the ribavirin group compared to placebo.
- Weighted severity scores suggest a potential long-term benefit of ribavirin, warranting further investigation in larger cohorts.
Objective:
To determine any long-term differences in adverse effects and pulmonary function between infants with respiratory syncytial virus and lower respiratory tract infection who were treated with ribavirin and a control group.
Study Design:
Long-term follow-up included enumeration of episodes of respiratory illness, wheezing, and pneumonia and, ultimately, administration of pulmonary function tests (PFTs). Pulse oximetry was done at each visit. During the first 3 years we conducted follow-up in the fall and spring. In years 4 and 5 we conducted 1 visit per year. During years 5 through 7 we conducted PFTs, and starting with year 7 a methacholine chloride challenge was done if forced expiratory volume in 1 second (FEV1) was greater than 70% of predicted value.
Results:
We prospectively enrolled (December 1983 to February 1985) in a randomized trial of ribavirin vs placebo children who were previously healthy, were premature, or had chronic pulmonary disease. One pulmonologist (R.F.; blinded) scored and interpreted the results of the PFTs. We studied 42 patients aged 1 to 33 months; 2 patients died (1 receiving ribavirin and 1 receiving placebo) and 5 patients receiving placebo were lost to follow-up; 35 patients (24 taking ribavirin and 11 taking placebo) attended 212 visits. Four patients were premature (3 in the ribavirin and 1 in the placebo group), and 3 of these had bronchopulmonary dysplasia (2 in the ribavirin and 1 in the placebo group). From years 1 to 3, there was more reactive airway disease, wheezing, and pneumonia in the placebo than in the ribavirin group (mean score, 22.3 for 12 placebo-treated patients vs. 15.8 for 23 ribavirin-treated patients; P = .07 by Kruskal-Wallis test); for all years, it was 22.0 for 11 placebo-treated patients vs. 16.0 for 22 ribavirin-treated patients (P = .10). After informed consent was given, 19 patients completed PFTs (13 receiving ribavirin and 6 receiving placebo); 7 of 13 ribavirin-treated patients (53%) had normal or mild PFT results vs. 0 of 6 placebo-treated patients (P = .04 by Fisher exact test). On methacholine challenge (7 ribavirin-treated patients and 5 placebo-treated patients), there was more reactivity in the placebo vs. the ribavirin group (exact P = .07). Scoring done by weighting for severity for 19 patients (13 ribavirin-treated patients and 6 placebo-treated patients) (even after correcting for asthma) showed a significant difference in favor of previously ribavirin-treated patients (exact P = .02).
Conclusions:
No outward effects were identified from ribavirin exposure. We observed no increase in reactive airway disease, wheezing, and pneumonia in the ribavirin compared with the placebo group. Weighted severity scores suggest long-term beneficial effect of ribavirin therapy; however, larger numbers should be evaluated.