scholarly journals Multi-centre, randomised non-inferiority trial of early treatment versus expectant management of patent ductus arteriosus in preterm infants (the BeNeDuctus trial): statistical analysis plan

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tim Hundscheid ◽  
Rogier Donders ◽  
Wes Onland ◽  
Elisabeth M. W. Kooi ◽  
Daniel C. Vijlbrief ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Pharmacological Treatment ◽  
Ductus Arteriosus ◽  
Expectant Management ◽  
The United States ◽  
Statistical Analysis Plan ◽  
Short Term ◽  
Patent Ductus

Abstract Background Controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants. A persistent PDA is associated with neonatal mortality and morbidity, but causality remains unproven. Although both pharmacological and/or surgical treatment are effective in PDA closure, this has not resulted in an improved neonatal outcome. In most preterm infants, a PDA will eventually close spontaneously, hence PDA treatment potentially increases the risk of iatrogenic adverse effects. Therefore, expectant management is gaining interest, even in the absence of convincing evidence to support this strategy. Methods/design The BeNeDuctus trial is a multicentre, randomised, non-inferiority trial assessing early pharmacological treatment (24–72 h postnatal age) with ibuprofen versus expectant management of PDA in preterm infants in Europe. Preterm infants with a gestational age of less than 28 weeks and an echocardiographic-confirmed PDA with a transductal diameter of > 1.5 mm are randomly allocated to early pharmacological treatment with ibuprofen or expectant management after parental informed consent. The primary outcome measure is the composite outcome of mortality, and/or necrotizing enterocolitis Bell stage ≥ IIa, and/or bronchopulmonary dysplasia, all established at a postmenstrual age of 36 weeks. Secondary short-term outcomes are comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. This statistical analysis plan focusses on the short-term outcome and is written and submitted without knowledge of the data. Trial registration ClinicalTrials.gov NTR5479. Registered on October 19, 2015, with the Dutch Trial Registry, sponsored by the United States National Library of Medicine Clinicaltrials.gov NCT02884219 (registered May 2016) and the European Clinical Trials Database EudraCT 2017-001376-28.

ASSOCIATION OF PATENT DUCTUS ARTERIOSUS SIZE WITH CLINICAL FEATURES AND SHORT-TERM OUTCOMES IN PRETERM INFANTS LESS THAN 34 WEEKS

2020 ◽  
Vol 07 (03) ◽  
pp. 105-108
Author(s):  
Chandrakala Bada Shekharappa ◽  
Edison Albert Balakrishnan Elizabeth ◽  
Bharathi Balachander
Keyword(s):  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Clinical Features ◽  
Ductus Arteriosus ◽  
Short Term ◽  
Patent Ductus

Using benchmarking to identify inter-centre differences in persistent ductus arteriosus treatment: can we improve outcome?

2017 ◽  
Vol 27 (8) ◽  
pp. 1488-1496 ◽  
Author(s):  
Esther J. S. Jansen ◽  
Koen P. Dijkman ◽  
Richard A. van Lingen ◽  
Willem B. de Vries ◽  
Daniel C. Vijlbrief ◽  
...  
Keyword(s):  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Standard Procedure ◽  
Ductus Arteriosus ◽  
Short Term ◽  
Surgical Ligation ◽  
Persistent Ductus Arteriosus ◽  
Ductal Closure ◽  
Neonatal Icu ◽  
Patent Ductus

AbstractObjectiveThe aim of this study was to identify inter-centre differences in persistent ductus arteriosus treatment and their related outcomes.Materials and methodsWe carried out a retrospective, multicentre study including infants between 24+0 and 27+6 weeks of gestation in the period between 2010 and 2011. In all centres, echocardiography was used as the standard procedure to diagnose a patent ductus arteriosus and to document ductal closure.ResultsIn total, 367 preterm infants were included. All four participating neonatal ICU had a comparable number of preterm infants; however, differences were observed in the incidence of treatment (33–63%), choice and dosing of medication (ibuprofen or indomethacin), number of pharmacological courses (1–4), and the need for surgical ligation after failure of pharmacological treatment (8–52%). Despite the differences in treatment, we found no difference in short-term morbidity between the centres. Adjusted mortality showed independent risk contribution of gestational age, birth weight, ductal ligation, and perinatal centre.ConclusionsUsing benchmarking as a tool identified inter-centre differences. In these four perinatal centres, the factors that explained the differences in patent ductus arteriosus treatment are quite complex. Timing, choice of medication, and dosing are probably important determinants for successful patent ductus arteriosus closure.

scholarly journals Baby-OSCAR: Outcome after Selective early treatment for Closure of patent ductus ARteriosus in preterm babies—a statistical analysis plan for short-term outcomes

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jennifer L. Bell ◽  
Samir Gupta ◽  
Edmund Juszczak ◽  
Pollyanna Hardy ◽  
Louise Linsell
Keyword(s):  
Statistical Analysis ◽  
Regression Models ◽  
Ductus Arteriosus ◽  
Statistical Analysis Plan ◽  
Short Term ◽  
Primary Analysis ◽  
Extremely Preterm ◽  
Postmenstrual Age ◽  
Preterm Babies ◽  
Patent Ductus

Abstract Background The Baby-OSCAR trial is a multi-centre, randomised, placebo-controlled parallel group trial of early treatment of large patent ductus arteriosus (PDA) with ibuprofen in extremely preterm infants. This paper describes the statistical analysis plan for the short-term health outcomes of the Baby-OSCAR trial. Methods and design This is a randomised controlled trial to determine if early-targeted treatment of a large PDA with parenteral ibuprofen in extremely preterm babies improves short and long-term health and economic outcomes. Infants born between 23+0 and 28+6 weeks of gestation, confirmed by echocardiography as having a large PDA (with a diameter of at least 1.5 mm and unrestricted pulsatile PDA flow pattern), with parental informed consent, were randomly allocated to receive either ibuprofen or placebo within 72 h of birth. The primary outcome is a composite of death by 36 weeks’ postmenstrual age or moderate or severe bronchopulmonary dysplasia (BPD) at 36 weeks’ postmenstrual age. Results Baseline demographic and clinical characteristics will be described by randomised group. The primary analysis will be on the modified intention to treat (ITT) population. Counts and percentages will be presented for binary and categorical variables, and mean and standard deviation or median and interquartile range will be presented for continuous variables. For binary outcomes, risk ratios and confidence intervals will be calculated using log binomial or Poisson regression with a robust variance estimator. Continuous outcomes will be analysed using linear regression models, or quantile regression models if skewed. Analyses will be adjusted for all minimisation factors where technically possible, and correlation between siblings from multiple births will be accounted for by nesting the clusters as a random effect. Both crude and adjusted effect estimates will be presented, with the primary inference based on the adjusted estimates. Ninety-five per cent confidence intervals will be used for all pre-specified outcome comparisons. Conclusion This paper describes the statistical analysis plan for short-term health outcomes of the trial, including the analysis principles, definitions of important outcomes, methods for primary analysis, pre-specified subgroup analysis, and secondary analysis. The plan was finalised prior to completion of short-term follow-up. Trial registration ISRCTN registry ISRCTN84264977. Registered on 15 September 2010.

scholarly journals Factors Associated With Benefit of Treatment of Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 9 ◽  
Author(s):  
Esther J. S. Jansen ◽  
Tim Hundscheid ◽  
Wes Onland ◽  
Elisabeth M. W. Kooi ◽  
Peter Andriessen ◽  
...  
Keyword(s):  
Birth Weight ◽  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Outcome Measures ◽  
Pharmacological Treatment ◽  
Meta Analysis ◽  
Ductus Arteriosus ◽  
Extremely Low Birth Weight ◽  
Grade 3 ◽  
Patent Ductus

Context: There is an ongoing debate on the optimal management of patent ductus arteriosus (PDA) in preterm infants. Identifying subgroup of infants who would benefit from pharmacological treatment might help.Objective: To investigate the modulating effect of the differences in methodological quality, the rate of open-label treatment, and patient characteristics on relevant outcome measures in randomized controlled trials (RCTs).Data Sources: Electronic database search between 1950 and May 2020.Study Selection: RCTs that assessed pharmacological treatment compared to placebo/no treatment.Data Extraction: Data is extracted following the PRISMA guidelines. Outcome measures were failure to ductal closure, surgical ligation, incidence of necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, periventricular leukomalacia, intraventricular hemorrhage (IVH) grade ≥3, retinopathy of prematurity and mortality.Results: Forty-seven studies were eligible. The incidence of IVH grade ≥3 was lower in the treated infants compared to the placebo/no treatment (RR 0.77, 95% CI 0.64–0.94) and in the subgroups of infants with either a gestational age <28 weeks (RR 0.77, 95% CI 0.61–0.98), a birth weight <1,000 g (RR 0.77, 95% CI 0.61–0.97), or if untargeted treatment with indomethacin was started <24 h after birth (RR 0.70, 95% CI 0.54–0.90).Limitations: Statistical heterogeneity caused by missing data and variable definitions of outcome parameters.Conclusions: Although the quality of evidence is low, this meta-analysis suggests that pharmacological treatment of PDA reduces severe IVH in extremely preterm, extremely low birth weight infants or if treatment with indomethacin was started <24 h after birth. No other beneficial effects of pharmacological treatment were found.

scholarly journals Predictive value of serum NT-proBNP concentrations for assessment hemodynamically significant patent ductus arteriosus in very preterm infants

2021 ◽  
pp. 28-36
Author(s):  
S.O. Potsiurko ◽  
◽  
D.O. Dobryanskyy ◽  
L.B. Sekretar ◽  
◽  
...  
Keyword(s):  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Predictive Value ◽  
Ductus Arteriosus ◽  
Randomized Study ◽  
Expectant Management ◽  
Very Preterm Infants ◽  
Very Preterm ◽  
Management Approaches ◽  
Patent Ductus

Hemodynamically significant patent ductus arteriosus (PDA) is a common complication in very preterm infants born at less than 32 weeks of gestation. At the same time, currently, there are no uniform criteria to identify the actual hemodynamic significance of PDA and generally accepted management approaches to such infants. Purpose — to assess the predictive value of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels for hemodynamically significant PDA in very preterm infants. Materials and methods. Fifty-two preterm infants with gestational age <32 weeks, chronological age <72 h, and PDA diameter >1.5 mm were involved in a randomized study. Twenty-seven (52%) of them were treated with ibuprofen or paracetamol starting within the first 3 days of life. Expectant management was applied to 25 (48%) infants. All patients underwent daily echocardiographic and two serum NT-proBNP measurements within the first 10 days after birth. According to the results of echocardiographic and clinical monitoring, 2 groups of patients were formed retrospectively. In 22 (42%) of them hemodynamically significant PDA (hsPDA) was diagnosed, and 30 (58%) had hemodynamically insignificant ductus arteriosus. Results. The percentage of infants who received pharmacological PDA treatment was not significantly different between the groups (p>0.05). Serum NT-proBNP concentrations at the median age of 2 and 8 days were significantly higher in infants with hsPDA (p<0.01). By the eighth day of life, the NT-proBNP level in both groups significantly decreased but remained considerably higher in newborns with hsPDA. Serum NT-proBNP concentrations on the second-third day of life could reliably predict hsPDA (AUC=0.93; 95% confidence interval: 0.86–1.0; p<0.05). Conclusions. Serum NT-proBNP concentrations on the second day of life >12000 pg/ml could reliably predict hsPDA. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of these Institutes. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: hemodynamically significant patent ductus arteriosus, PDA, NT-proBNP, prognostic value, very preterm infants.

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