Best Evidence Topics

Randomised control trial

Dregelid E, Heldal K, Andersen K, Stangeland L, Svendsen E.
Dilation of the internal mammary artery by external papaverine application to the pedicle: an improved method.
Eur J Cardiothorac Surg
  • Submitted by:Sachin Shah - Fellow
  • Institution:Hospital for Sick Children and University of Toronto
  • Date submitted:12th June 2003
Before CA, i rated this paper: 8/10
1 Objectives and hypotheses
1.1 Are the objectives of the study clearly stated?
  Yes. The objective was to determine whether early intervention with high frequency ventilation reduced mortality and chronic lung disease amongst newborns with gestational age of 28 weeks or less.
2 Design
2.1 Is the study design suitable for the objectives
  Yes. Multicenter, randomised controlled trial
2.2 Who / what was studied?
  Infants between 23-28 weeks gestation and needing intubation since birth. Infants with major congenital malformations and those needing transfer to some other hospital were excluded from the trial.
2.3 Was this the right sample to answer the objectives?
2.4 Is the study large enough to achieve its objectives? Have sample size estimates been performed?
  Yes. Sample size estimates were performed. The assumption was that incidence of CLD or mortality would be 75% for the lower gestational age and 48% for the higher gestational age. With a sample size of 800, the study had 90% power (at a significance level of 0.05) to detect a difference between 2 groups of 9-11 percentage points.
2.5 Were all subjects accounted for?
  Yes. 870 infants were randomised. Of these 66 were ineligible (27 dies, 23 did not need ventilation, 13 > 28 weeks GA, 3 had other reasons). 7 infants withdrew after entry (5 deemed ineligible, 2 withdrawn at parents' request).
797 infants included in the trial (400 in HFOV group, 397 in CV group).
2.6 Were all appropriate outcomes considered?
  Yes. Outcomes were CLD, death, airleaks, PIE, IVH, PVL, PDA, NEC, ROP, NEC, Duration of hospital stay, Need for postnatal steroids, etc
The infants were stratified into 2 groups; 23-25 weeks and 26-28 weeks.
2.7 Has ethical approval been obtained if appropriate?
  Yes. The study was approved by the research-ethics committee at each participating center.
2.8 Were the patients randomised between treatments?
2.9 How was randomisation carried out?
  Infants were randomly assigned in blocks of 4 to either CV or HFOV, with stratification according to gestational age and according to centre.
2.10 Are the outcomes clinically relevant?
  Yes. All important outcomes are considered.
3 Measurement and observation
3.1 Is it clear what was measured, how it was measured and what the outcomes were?
  Primary outcome was composite of death or CLD ( defined by dependence on supplemental oxygen at 36 weeks CGA).
Secondary outcome measures were age at death, age at hospital discharge, major abnormality on cranial ultrasonography, air leak, failure of treatment, failure on hearing test, PDA and ROP
3.2 Are the measurements valid?
3.3 Are the measurements reliable?
  Standard objective tests were used to used to measure the outcomes
3.4 Are the measurements reproducible?
3.5 Were the patients and the investigators blinded?
  The investigators were not blinded to the type of ventilator.
4 Presentation of results
4.1 Are the basic data adequately described?
  Yes. Clinical characteristics which are described include birth weight, gestational age, antenatal corticosteroids, maternal chorioamnionitis, duration of rupture of membranes, maternal GBS status, PIH, toxemia, race, antenatal care, use of illicit drugs, number of caesarean sections, multiple births, sex of infant, apgar scores,need for surfactant, indomethacin and need for resuscitation.
4.2 Were groups comparable at baseline?
  Yes. There was no difference in the characteristics described above
4.3 Are the results presented clearly, objectively and in sufficient detail to enable readers to make their own judgement?
  Yes. The results are presented as relative risk with 95% confidence intervals.
4.4 Are the results internally consistent, i.e. do the numbers add up properly?
4.5 Were side effects reported?
  All important side-effects were reported such as Intraventricular hemorrhage, periventricular leucomalacia, pneumothorax, patent ductus arteriosus, necrotising enterocolitis, retinopathy of prematurity and hearing loss.
Long term followup is planned for the infants in the study
5 Analysis
5.1 Are the data suitable for analysis?
5.2 Are the methods appropriate to the data?
5.3 Are any statistics correctly performed and interpreted?
  Relative risks with 95% confidence intervals were calculated to estimate the relative effect of HFOV as compared to that of CV for all outcomes. Logistic regression was used to investigate treatment effects with the use of gestational age and study location as covariates. Also clinically important covariates were included in the model.
6 Discussion
6.1 Are the results discussed in relation to existing knowledge on the subject and study objectives?
6.2 Is the discussion biased?
  No. The discussion is appropriately balanced.
7 Interpretation
7.1 Are the authors' conclusions justified by the data?
  Yes. The authors conclude that results obtained with HFOV and CV do not differ significantly in early treatment fo respiratory distress in very preterm infants. Assessment of long term effects will require additional follow-up.
7.2 What level of evidence has this paper presented? (using CEBM levels)
  Level 1b
7.3 Does this paper help me answer my problem?
After CA, i rated this paper: 10/10
8 Implementation
8.1 Can any necessary change be implemented in practice?
  No change needs to be implemented in the current practice
8.2 What aids to implementation exist?
  Safety of HFOV. No increase in adverse effects.
8.3 What barriers to implementation exist?
  No clinical benefit of HFOV over CV.
Long term follow up needed