In a double blind randomised controlled trial, 30 infants with chronic lung disease received fluticasone propionate or placebo for one year. There were no significant differences between treatment groups in the incidence of any day or night time symptoms or any other outcome measure

Beresford, M.W.

Primhak, R.A.

Shaw, N.J.

Subhedar, N.V.

English

PubMed

M W Beresford

Crossref

Randomised double blind placebo controlled trial of inhaled fluticasone propionate in infants with chronic lung disease

White Rose Research Online

This is a repository copy of Randomised double blind placebo controlled trial of inhaled fluticasone propionate in infants with chronic lung disease.White Rose Research Online URL for this paper:http://eprints.whiterose.ac.uk/550/Article:Beresford, M.W., Primhak, R.A., Subhedar, N.V. et al. (1 more author) (2002) Randomised double blind placebo controlled trial of inhaled fluticasone propionate in infants with chronic lung disease. Archives of Disease in Childhood Fetal and Neonatal Edition, 87 (1). F62-F63. ISSN 1359-2998 https://doi.org/10.1136/fn.87.1.F62eprints@whiterose.ac.ukhttps://eprints.whiterose.ac.uk/Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version - refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher’s website. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. SHORT REPORTRandomised double blind placebo controlled trial ofinhaled fluticasone propionate in infants with chroniclung diseaseM W Beresford, R Primhak, N V Subhedar, N J Shaw. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Arch Dis Child Fetal Neonatal Ed 2002;87:F62–F63In a double blind randomised controlled trial, 30 infantswith chronic lung disease received fluticasone propionateor placebo for one year. There were no significantdifferences between treatment groups in the incidence ofany day or night time symptoms or any other outcomemeasures.Chronic lung disease of prematurity (CLD) is associatedwith significant respiratory morbidity in the early yearsof life.1 2 Systemic corticosteroids reduce the duration ofrespiratory support in infants at risk of developing CLD.3Inhaled corticosteroids reduce symptoms in wheezinginfants.4 No randomised controlled studies have assessed theefficacy of inhaled corticosteroids as prophylactic therapy inCLD. We report the results of a randomised double blind pla-cebo controlled trial of inhaled fluticasone propionate ininfants with CLD, which aimed to determine whether theregular use of an inhaled corticosteroid reduces respiratorymorbidity.Infants studied required supplementary oxygen at 36 post-menstrual weeks. They were excluded if they were ventilatedor receiving systemic corticosteroids at this time. Localresearch ethics approval was granted and written informedparental consent obtained. Infants were randomised to receive250 µg twice daily of inhaled fluticasone propionate or placebovia metered dose inhaler (with spacer and face mask) for a oneyear study period. Treatment allocation was double blinded.Primary outcome was the incidence of reported symptom freedays. Secondary outcomes included symptom frequency(assessed using a symptom diary), growth parameters, andhospital admissions. It was estimated that placebo treatedinfants may experience symptoms on 50% of days. Sample sizecalculation, looking for a 20% reduction in symptomfrequency in fluticasone treated infants (80% power, 95% con-fidence) revealed that 63 infants were required in each treat-ment arm. After two years recruitment, it became evident thatthe original sample size would not be achieved in a reasonabletime. A decision was taken to stop the trial but to report avail-able data for use in designing future studies or systematicreviews.Thirty infants were randomised to the study; 15 receivedfluticasone (table 1). Two infants in the fluticasone treatedgroup and three in the placebo arm withdrew from the trialwithout completing diaries. Three infants had no symptomdiaries complete despite continuing treatment, one from thefluticasone arm and two from the placebo arm of the trial.There were no significant differences between treatmentgroups in the incidence of any day or night time symptoms(table 2). The median (interquartile range) duration ofcontinuous oxygen therapy was 181 days (133–301) for fluti-casone and 119 days (56–280) for placebo treated infants(p = 0.4), while the median duration of inhaler usage was 350days (113–373) and 242 days (97–301) respectively (p = 0.4).Table 1 Patient characteristicsFluticasone (n=15) Placebo (n=15)Male 8 (53%) 9 (60%)Gestation (wk) 27 (25 to 28) 28 (27 to 30)Birth weight (g) 864 (755 to 1058) 1120 (820 to 1430)Z score 0.17 (−0.43 to 0.84) −0.21 (−0.45 to 0.57)Birth OFC (cm) 25.2 (23.8 to 30) 26.2 (23.5 to 28.6)Z score 0.24 (−1.18 to 1.17) 0.06 (−0.95 to 0.50)Respiratory supportTotal ventilated days 17 (13 to 34) 15 (7 to 25)Maximum PIP (cmH2O) 25 (20 to 28) 26 (20 to 32)Maximum (FiO2 (%) 71 (55 to 100) 100 (70 to 100)Characteristics at recruitmentAge (corrected weeks) 39 (38 to 43) 40 (37 to 42)Weight (g) 2458 (2100 to 2870) 2390 (2042 to 2637)Z score −1.57 (−3.05 to −1.01) −1.76 (−2.70 to −1.27)OFC (cm) 33.6 (32.2 to 35.5) 33.5 (32.4 to 34.0)Z score −0.55 (−2.46 to 0.78) −0.77 (−1.56 to 0.29)Supplemental oxygen (l/min) 0.25 (0.1 to 0.4) 0.15 (0.05 to 0.3)Results expressed as median (interquartile range).OFC, occipitofrontal circumference; PIP, peak inspiratory pressure; FiO2, fractional inspired oxygen.F62www.archdischild.comThere was no significant difference between treatment groupswith respect to weight gain expressed as Z score or increase inhospital admissions for respiratory illness, number of coursesof oral corticosteroids, or the use of bronchodilator therapyduring the study period.Fluticasone is a potent inhaled corticosteroid5 and the lackof a major clinical effect might be a result of poor treatmentadherence, an insensitive outcome measure, or a type II error.Double blinding of participants optimised the chance ofdetecting a significant treatment effect. Stratification bycentre compensated for potential variation in managementregimes. Efficacy of an inhaled prophylactic therapy dependson adequate and regular administration. Parents were trainedin the inhaler technique and regularly monitored. Being apragmatic trial, no objective measure of treatment adherence(for example, weighing of canisters) was adopted. Use ofsymptom diaries, though easy to complete and regularlysupervised, relies on parental motivation and interpretation ofsymptoms. The eight infants either withdrawing or not com-pleting symptom diaries were excluded from analyses. No datawere available for the primary outcome measure and thereforethey could not be included in an intention to treat analysis.This study provides useful data regarding respiratory symp-tomatology in placebo treated infants with CLD. Approxi-mately 19% of infants with CLD treated with placebo hadshort episodes of cough or wheeze during the day and 20%had similar episodes sufficient to wake them at least once atnight. These are substantially lower frequencies than our esti-mated values for sample size calculation (50%) and indicatethat a much larger sample size would be need to detect impor-tant differences in symptom frequency in this population.In conclusion, this is a small, negative outcome study thatdoes not encourage clinicians to start inhaled corticosteroidsprophylactically in infants with CLD. A larger clinical trial oftreatment in symptomatic children with CLD would be thenext appropriate step.ACKNOWLEDGEMENTWe thank Allen and Hanburys for supplying the inhalers and diaries.. . . . . . . . . . . . . . . . . . . . .Authors’ affiliationsM W Beresford, N V Subhedar, N J Shaw, Royal Liverpool Children’sNHS Trust, Alder Hey, UKR Primhak, Sheffield Children’s Hospital NHS Trust, UKCorrespondence to: Dr N J Shaw, Neonatal Unit, Liverpool Women’sHospital, Liverpool L8 7SS, UK; ben.shaw@lwh-tr.nwest.nhs.ukAccepted 19 February 2002REFERENCES1 Sauve R S, Singhal N. Long-term morbidity of infants withbronchopulmonary dysplasia. Pediatrics 1985;76:725–33.2 Bhutani V K, Abbasi S. Long-term pulmonary consequences in survivorswith bronchopulmonary dysplasia. Clin Perinatol 1992;19:649–71.3 Halliday HL, Ehrenkranz RA. Delayed (>3 weeks) postnatalcorticosteroids for chronic lung disease in preterm infants (Cochranereview). In: The Cochrane Library, Issue 2. Oxford: Update Software,2001.4 Bisgaard H, Munck S, Nielsen J, et al. Inhaled budesonide for treatmentof recurrent wheezing in early childhood. Lancet 1990;336:649–51.5 Harding SM. The human pharmacology of fluticasone propionate. RespirMed 1990;84(suppl A):25–9.Table 2 Incidence of respiratory symptoms reported in diariesFluticasone (n=12) Placebo (n=10) p valueData days per patient 296 (66 to 358) 220 (85 to 313) 0.42Incidence of day time symptoms (% days)None 67 (50 to 85) 81 (48 to 97) 0.50One or more episodes 33 (15 to 50) 19 (3 to 52) 0.50Two or more episodes 11 (3 to 25) 7 (0 to 20) 0.37Reliever used during day 1 (0 to 12) 3 (0 to 12) 0.72Incidence of night time symptoms (% nights)None 76 (58 to 94) 80 (44 to 95) 0.87Woke once or more 24 (6 to 42) 20 (5 to 56) 0.87Woke twice or more 6 (4 to 20) 7 (9 to 37) 0.67Reliever used at night 4 (0 to 26) 1 (0 to 6) 0.50Results expressed as median (interquartile range).Fluticasone propionate in infants with chronic lung disease F63www.archdischild.com

Randomised double blind placebo controlled trial of

inhaled fluticasone propionate in infants with chronic

lung disease

In a double blind randomised controlled trial, 30 infants with chronic lung disease received fluticasone propionate or placebo for one year. There were no significant differences between treatment groups in the incidence of any day or night time symptoms or any other outcome measures

Randomised double blind placebo controlled trial of inhaled fluticasone propionate in infants with chronic lung disease

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