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 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.

scholarly journals Study protocol: baby-OSCAR trial: Outcome after Selective early treatment for Closure of patent ductus ARteriosus in preterm babies, a multicentre, masked, randomised placebo-controlled parallel group trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Samir Gupta ◽  
◽  
Edmund Juszczak ◽  
Pollyanna Hardy ◽  
Nimish Subhedar ◽  
...  
Keyword(s):  
Ductus Arteriosus ◽  
Parallel Group ◽  
Extremely Preterm ◽  
Postmenstrual Age ◽  
Preterm Babies ◽  
Short And Long Term ◽  
Parallel Group Trial ◽  
Group Trial ◽  
Patent Ductus

Abstract Background The question of whether to treat patent ductus arteriosus (PDA) early or wait until symptoms appear remains high on the research agenda for neonatal medicine. Around 7000 extremely preterm babies under 29 weeks’ gestation are born in the UK every year. In 40% of cases the PDA will fail to close spontaneously, even by 4 months of age. Untreated PDA can be associated with several serious and life-threatening short and long-term complications. Reliable data to support clinical decisions about PDA treatment are needed to prevent serious complications in high risk babies, while minimising undue exposure of infants. With the availability of routine bedside echocardiography, babies with a large PDA can be diagnosed before they become symptomatic. Methods This is a multicentre, masked, randomised, placebo-controlled parallel group trial to determine if early-targeted treatment of a large PDA with parenteral ibuprofen in extremely preterm babies (23+ 0–28+ 6 weeks’ gestation) improves short and long-term health and economic outcomes. With parental informed consent, extremely preterm babies (born between 23+ 0–28+ 6 weeks’ gestation) admitted to tertiary neonatal units are screened using echocardiography. Babies with a large PDA on echocardiography, defined by diameter of at least 1.5 mm and unrestricted pulsatile PDA flow pattern, are randomly allocated to either ibuprofen or placebo within 72 h of birth. The primary endpoint is the composite outcome of death by 36 weeks’ postmenstrual age or moderate or severe bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age. Discussion Prophylactic pharmacological treatment of all preterm babies unnecessarily exposes them to potentially serious side effects of drug treatment, when their PDA may have closed spontaneously. However, delaying treatment until babies become symptomatic could result in loss of treatment benefit as irreversible damage may have already been done. Targeted, early pharmacological treatment of PDA in asymptomatic babies has the potential to overcome the disadvantages of both prophylactic (overtreatment) and symptomatic approaches (potentially too late). This could result in improvements in the clinically important short-term clinical (mortality and moderate or severe BPD at 36 weeks’ postmenstrual age) and long-term health outcomes (moderate or severe neurodevelopment disability and respiratory morbidity) measured at 2 years corrected age. Trial registration ISRCTN84264977. Date assigned: 15/09/2010.

scholarly journals Detailed statistical analysis plan for the SafeBoosC III trial: a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants

Trials ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Mathias Lühr Hansen ◽  
Adelina Pellicer ◽  
Christian Gluud ◽  
Eugene Dempsey ◽  
Jonathan Mintzer ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Gestational Age ◽  
Cerebral Oxygenation ◽  
Statistical Analysis Plan ◽  
Primary Analysis ◽  
Treatment As Usual ◽  
Extremely Preterm ◽  
Detailed Statistical Analysis ◽  
Oxygenation Monitoring ◽  
Intra Class Correlation Coefficient

Abstract Background Infants born extremely preterm are at high risk of dying or suffering from severe brain injuries. Treatment guided by monitoring of cerebral oxygenation may reduce the risk of death and neurologic complications. The SafeBoosC III trial evaluates the effects of treatment guided by cerebral oxygenation monitoring versus treatment as usual. This article describes the detailed statistical analysis plan for the main publication, with the aim to prevent outcome reporting bias and data-driven analyses. Methods/design The SafeBoosC III trial is an investigator-initiated, randomised, multinational, pragmatic phase III trial with a parallel group structure, designed to investigate the benefits and harms of treatment based on cerebral near-infrared spectroscopy monitoring compared with treatment as usual. Randomisation will be 1:1 stratified for neonatal intensive care unit and gestational age (lower gestational age (< 26 weeks) compared to higher gestational age (≥ 26 weeks)). The primary outcome is a composite of death or severe brain injury at 36 weeks postmenstrual age. Primary analysis will be made on the intention-to-treat population for all outcomes, using mixed-model logistic regression adjusting for stratification variables. In the primary analysis, the twin intra-class correlation coefficient will not be considered. However, we will perform sensitivity analyses to address this. Our simulation study suggests that the inclusion of multiple births is unlikely to significantly affect our assessment of intervention effects, and therefore we have chosen the analysis where the twin intra-class correlation coefficient will not be considered as the primary analysis. Discussion In line with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines, we have developed and published this statistical analysis plan for the SafeBoosC III trial, prior to any data analysis. Trial registration ClinicalTrials.org, NCT03770741. Registered on 10 December 2018.

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

scholarly journals The Effect of Remittances on Poverty in the Emerging Countries of the European Union

2019 ◽  
Vol 11 (12) ◽  
pp. 3265 ◽  
Author(s):  
Anca Mehedintu ◽  
Georgeta Soava ◽  
Mihaela Sterpu
Keyword(s):  
European Union ◽  
Statistical Analysis ◽  
Economic Crisis ◽  
Regression Models ◽  
Emerging Countries ◽  
Time Dependent ◽  
The European Union ◽  
Short Term ◽  
Growth Trend ◽  
Poverty Threshold

In this paper we study the evolution of remittances and risk of poverty threshold for nine emerging countries in the European Union and analyzed the evolution and trend of the share of remittances in the risk of poverty threshold. The analysis was performed on data taken from the Eurostat database for the period 2005–2017. The statistical analysis of the data showed that the evolution of both remittances and risk of poverty threshold was heavily influenced by the global economic crisis. Although after the crisis, the risk of poverty threshold has seen a growing trend in all emerging countries, the remittances have experienced sinuous variations, dramatic declines for some of the countries (drastically for Romania and Latvia) and significant increases for others (Hungary). The results of the analysis using time-dependent regression models lead to the conclusion that, although the share of remittances in risk of poverty threshold diminished abruptly after the 2009 economic crisis, in the short term it is expected to maintain a growth trend for most of the analyzed countries (Bulgaria, Czechia, Hungary, Lithuania, Poland, Romania, and Slovakia), followed downward tendency after 2018 for Bulgaria and Romania, and after 2020 for Hungary and Lithuania. For Latvia and Estonia, both quadratic and cubic models estimate a decreasing evolution.

Hypertrophic cardiomyopathy in an extremely preterm infant

2021 ◽  
Vol 14 (3) ◽  
pp. e239787
Author(s):  
Apoorva Aiyengar ◽  
Claire Howarth ◽  
Sujith Pereira
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Patent Ductus Arteriosus ◽  
Preterm Infant ◽  
Preterm Infants ◽  
Ductus Arteriosus ◽  
Careful Consideration ◽  
Differential Diagnoses ◽  
Cardiac Remodelling ◽  
Extremely Preterm ◽  
Patent Ductus

We present a case of an extreme preterm infant (Baby X) born at 24-week gestation. The echocardiogram showed evidence of hypertrophic cardiomyopathy (HCM) and a patent ductus arteriosus (PDA). There are a number of well-known causes of neonatal HCM including genetic, metabolic and endocrine. PDA is commonly present in preterm infants, and this can contribute to cardiac remodelling and result in cardiac changes mimicking HCM. Furthermore, medications such as steroids can also cause HCM through various mechanisms. A careful consideration of all the different aetiologies for HCM is important for appropriate management of such cases. This report examines the evidence in the literature for the above differential diagnoses and highlights the challenges in diagnosing the underlying cause of HCM in a preterm infant.

scholarly journals Conservative Non-intervention Approach for Hemodynamically Significant Patent Ductus Arteriosus in Extremely Preterm Infants

2020 ◽  
Vol 8 ◽  
Author(s):  
Se In Sung ◽  
Yun Sil Chang ◽  
So Yoon Ahn ◽  
Heui Seung Jo ◽  
Misun Yang ◽  
...  
Keyword(s):  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Ductus Arteriosus ◽  
Intervention Approach ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Surgical Treatments ◽  
Minimal Evidence ◽  
Patent Ductus

While persistent patent ductus arteriosus (PDA) in preterm infants has been known to be associated with increased mortality and morbidities including bronchopulmonary dysplasia, and necrotizing enterocolitis, there is minimal evidence supporting their causal relationships, and most traditional medical and/or surgical treatments have failed to show improvements in these outcomes. As such, the pendulum has swung toward the conservative non-intervention approach for the management of persistent PDA during the last decade; however, the benefits and risks of this approach are unclear. In this mini review, we focused on whom, when, and how to apply the conservative non-intervention approach for persistent PDA, especially in extremely preterm infants.

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