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Efficacy and safety of deferoxamine, deferasirox and deferiprone triple iron chelator combination therapy for transfusion-dependent β-thalassaemia with very high iron overload: a protocol for randomised controlled clinical trial
Premawardhena, A., Perera, C., Wijethilaka, M. N., Wanasinghe, S. K., Rajakaruna, Rhmg, Samarasinghe, Rankk, Williams, S., Mettananda, S.
BMJ open. 2024;14(2):e077342
Abstract
INTRODUCTION Despite the improvement in medical management, many patients with transfusion-dependent β-thalassaemia die prematurely due to transfusion-related iron overload. As per the current guidelines, the optimal chelation of iron cannot be achieved in many patients, even with two iron chelators at their maximum therapeutic doses. Here, we evaluate the efficacy and safety of triple combination treatment with deferoxamine, deferasirox and deferiprone over dual combination of deferoxamine and deferasirox on iron chelation in patients with transfusion-dependent β-thalassaemia with very high iron overload. METHODS AND ANALYSIS This is a single-centre, open-label, randomised, controlled clinical trial conducted at the Adult and Adolescent Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Patients with haematologically and genetically confirmed transfusion-dependent β-thalassaemia are enrolled and randomised into intervention or control groups. The intervention arm will receive a combination of oral deferasirox, oral deferiprone and subcutaneous deferoxamine for 6 months. The control arm will receive the combination of oral deferasirox and subcutaneous deferoxamine for 6 months. Reduction in iron overload, as measured by a reduction in the serum ferritin after completion of the treatment, will be the primary outcome measure. Reduction in liver and cardiac iron content as measured by T2* MRI and the side effect profile of trial medications are the secondary outcome measures. ETHICS AND DISSEMINATION Ethical approval for the study has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (Ref. P/06/02/2023). The trial results will be disseminated in scientific publications in reputed journals. TRIAL REGISTRATION NUMBER The trial is registered in the Sri Lanka Clinical Trials Registry (Ref: SLCTR/2023/010).
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High-dose intravenous immunoglobulin versus albumin 4% in paediatric toxic shock syndrome: a randomised controlled feasibility study
Portefaix, A., Dhelens, C., Recher, M., Cour-Andlauer, F., Naudin, J., Mortamet, G., Joram, N., Tissières, P., Ginhoux, T., Kassai, B., et al
Archives of disease in childhood. 2024
Abstract
PURPOSE Toxic shock syndrome (TSS) is a rare disease responsible for significant morbidity and mortality. Intravenous immunoglobulin (IG) therapy in paediatric TSS could improve shock and organ failure, but more consistent efficacy and safety data are needed. Our objective was to determine whether a randomised clinical trial (RCT) assessing intravenous IG in TSS in children is feasible. METHODS We performed a multicentre, feasibility, double-blind RCT assessing efficacy of high-dose intravenous IG versus albumin 4% (control group) within the first 12 hours of shock onset. Included patients were aged above 1 month and below 18 years with suspected TSS and septic shock. Feasibility was assessed by measuring inclusion rate, protocol compliance and missing data regarding death and the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) Score. Other secondary clinical outcomes were evaluated during hospital stay, at 60 day and 1 year. RESULTS 28 patients, admitted in 6 paediatric intensive care units during 36 consecutive months and followed for 1 year, received the allocated treatment: 13 in intravenous IG group, 15 in control group. The median age was 10.6 years and the sex ratio was 1. Inclusion rate was above 50%, protocol deviations were below 30% and missing data regarding death and PELOD-2 Score below 10%. No difference concerning secondary clinical outcomes between groups was observed, and more adverse events were reported in the control group. CONCLUSION It seems to be feasible to conduct an RCT assessing intravenous IG efficacy and safety in paediatric TSS but must be realised internationally, with choice of a clinically relevant endpoint and a specific design in order to be realistic. TRIAL REGISTRATION NUMBER NCT02219165.
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Cardiac assessment and inflammatory markers in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV2 (PIMS-TS) treated with methylprednisolone versus intravenous immunoglobulins: 6-month follow-up outcomes of the randomised controlled Swissped RECOVERY trial
Andre, M. C., Sanchez, C., Bressieux-Degueldre, S., Perez, M. H., Wütz, D., Blanchard-Rohner, G., Grazioli, S., Schöbi, N., Trück, J., Welzel, T., et al
EClinicalMedicine. 2024;67:102358
Abstract
BACKGROUND Previous findings from the Swissped RECOVERY trial showed that patients with Pediatric Inflammatory Multisystem Syndrome-Temporally Associated with SARS-CoV-2 (PIMS-TS) who were randomly assigned to intravenous immunoglobulins or methylprednisolone have a comparable length of hospital stay. Here, we report the 6-month follow-up outcomes of cardiac pathologies and normalisation of clinical or laboratory signs of inflammation from this study population. METHODS This pre-planned follow-up of patients with PIMS-TS included the Swissped RECOVERY Trial reports on the 6-month outcomes of the cohort after randomisation, with a focus on cardiac, haematological, and biochemical findings. The trial was an investigator-initiated randomised multicentre open-label two-arm trial in children and adolescents hospitalised with PIMS-TS at ten hospitals in Switzerland. Cardiological assessments and laboratory analyses were prospectively collected in the intention-to-treat analysis on pre-defined intervals after hospital discharge. Differences between randomised arms were investigated using Chi-square test for categorical and Wilcoxon test for continuous variables. The trial is registered with the Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588). FINDINGS Between May 21, 2021 and April 15, 2022, 75 patients with a median age of 9.1 years (IQR 6.2-12.2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulin group). During follow-up, the incidence of abnormal left ventricular systolic function, coronary artery aneurysms (CAA), and other signs of inflammation were comparable in both groups. However, we detected cardiac abnormalities with low incidence and a mild degree grade of pathology. CAAs were observed in 2/38 children (5.3%) in the IVIG group and 1/37 children (2.7%) in the methylprednisolone group at 6-month follow-up (difference proportion 0.75; 95% confidence interval (CI) -0.05 to 1.0; p = 0.39). INTERPRETATION Methylprednisolone alone may be an acceptable first-line treatment as left ventricular systolic dysfunction and clinical/laboratory evidence for inflammation quickly resolved in all children. However, our findings need further confirmation through larger studies as our sample size is likely to be of insufficient power to address rare clinically relevant adverse outcomes. FUNDING NOMIS, Vontobel, and Gaydoul Foundation.
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Immunomodulatory therapy in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS, MIS-C; RECOVERY): a randomised, controlled, open-label, platform trial
The Lancet. Child & adolescent health. 2024
Abstract
BACKGROUND Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS), also known as multisystem inflammatory syndrome in children (MIS-C) emerged in April, 2020. The paediatric comparisons within the RECOVERY trial aimed to assess the effect of intravenous immunoglobulin or corticosteroids compared with usual care on duration of hospital stay for children with PIMS-TS and to compare tocilizumab (anti-IL-6 receptor monoclonal antibody) or anakinra (anti-IL-1 receptor antagonist) with usual care for those with inflammation refractory to initial treatment. METHODS We did this randomised, controlled, open-label, platform trial in 51 hospitals in the UK. Eligible patients were younger than 18 years and had been admitted to hospital for PIMS-TS. In the first randomisation, patients were randomly assigned (1:1:1) to usual care (no additional treatments), usual care plus methylprednisolone (10mg/kg per day for 3 consecutive days), or usual care plus intravenous immunoglobulin (a single dose of 2 g/kg). If further anti-inflammatory treatment was considered necessary, children aged at least 1 year could be considered for a second randomisation, in which patients were randomly assigned (1:2:2) to usual care, intravenous tocilizumab (12 mg/kg in patients <30 kg; 8mg/kg in patients ≥30 kg, up to a maximum dose of 800 mg), or subcutaneous anakinra (2 mg/kg once per day in patients ≥10 kg). Randomisation was by use of a web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was duration of hospital stay. Analysis was by intention to treat. For treatments assessed in each randomisation, a single Bayesian framework assuming uninformative priors for treatment was used to jointly assess the efficacy of each intervention compared with usual care. The trial was registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS Between May 18, 2020, and Jan 20, 2022, 237 children with PIMS-TS were enrolled and included in the intention-to-treat analysis. Of the 214 patients who entered the first randomisation, 73 were assigned to receive intravenous immunoglobulin, 61 methylprednisolone, and 80 usual care. Of the 70 children who entered the second randomisation (including 23 who did not enter the first randomisation), 28 were assigned to receive tocilizumab, 14 anakinra, and 28 usual care. Mean age was 9·5 years (SD 3·8) in the randomisation and 9·6 years (3·6) in the second randomisation. 118 (55%) of 214 patients in the first randomisation and 39 (56%) of 70 patients in the second randomisation were male. 130 (55%) of 237 patients were Black, Asian, or minority ethnic, and 105 (44%) were White. Mean duration of hospital stay was 7·4 days (SD 0·4) in children assigned to intravenous immunoglobulin and 7·6 days (0·4) in children assigned to usual care (difference -0·1 days, 95% credible interval [CrI] -1·3 to 1·0; posterior probability 59%). Mean duration of hospital stay was 6·9 days (SD 0·5) in children assigned to methylprednisolone (difference from usual care -0·7 days, 95% CrI -1·9 to 0·6; posterior probability 87%). Mean duration of hospital stay was 6·6 days (SD 0·7) in children assigned to second-line tocilizumab and 9·9 days (0·9) in children assigned to usual care (difference -3·3 days, 95% CrI -5·6 to -1·0; posterior probability >99%). Mean duration of hospital stay was 8·5 days (SD 1·2) in children assigned to anakinra (difference from usual care -1·4 days, 95% CrI -4·3 to 1·8; posterior probability 84%). Two persistent coronary artery aneurysms were reported among patients assigned to usual care in the first randomisation. There were few cardiac arrythmias, bleeding, or thrombotic events in any group. Two children died; neither was considered related to study treatment. INTERPRETATION Moderate evidence suggests that, compared with usual care, first-line intravenous methylprednisolone reduces duration of hospital stay for children with PIMS-TS. Good evidence suggests that second-line tocilizumab reduces duration of hospital stay for children with inflammation refractory to initial treatment. Neither intravenous immunoglobulin nor anakinra had any effect on duration of hospital stay compared with usual care. FUNDING Medical Research Council and National Institute of Health Research.
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The Effect of Tranexamic Acid and Controlled Hypotension on Perioperative Blood Loss in Craniosynostosis Surgery
Moradi Farsani, D., Mazaheri, Z., Shafa, A.
Anesthesiology and pain medicine. 2023;13(1):e130462
Abstract
BACKGROUND Open cranial vault reconstruction is the standard technique of craniosynostosis correction that may cause significant blood loss. OBJECTIVES The current study aimed at comparing the effect of tranexamic acid (TXA), controlled hypotension, and their combination on perioperative blood loss and transfusion requirement in craniosynostosis surgery. METHODS The present randomized, double-blind clinical trial was conducted on 75 infants referred for craniosynostosis surgery during 2017 - 2018. Ten minutes before the start of surgery, 10 mg/kg of TXA was administered intravenously to patients in the first group (TXA group). In the second group, patients were subjected to the controlled hypotension anesthesia (CHA) using intravenous remifentanil 0.1 μ/kg (CHA group). In the third group, the patients underwent CHA similar to that of the second group, along with intravenous injection of 10 mg/kg of TXA (CHA-TXA group). Then, patients' mean arterial pressure (MAP), heart rate (HR), total blood loss, and transfusion volume were evaluated and recorded. RESULTS The results of the present study revealed that although the changes in MAP and HR parameters over time (three hours after surgery) were significant in all three groups, the lowest decrease was observed in the CHA-TXA group (P-value < 0.05). In addition, the total perioperative blood loss in the CHA-TXA group with the mean of 181.20 ± 82.71 cc was significantly less than the total perioperative blood loss in the CHA and TXA groups with the means of 262.00 ± 104.04 cc and 212.80 ± 80.75 cc, respectively (P-value < 0.05). Moreover, the transfusion volume in the CHA-TXA group with the mean of 112.40 ± 53.50 cc was significantly lower than the transfusion volume in the CHA and TXA groups with the means of 174.00 ± 73.93 cc and 160.63 ± 59.35 cc, respectively (P-value < 0.05). In contrast, the total blood loss and transfusion volume were not significantly different between the CHA and TXA groups (P-value > 0.05). CONCLUSIONS According to the results of the present study, although the administration of TXA alone could effectively prevent blood loss and was associated with fewer transfusion requirements, the combination of this approach with hypotensive anesthesia resulted in more reduction in perioperative blood loss and transfusion volume as well as better hemodynamic stability.
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Effect of red blood cell storage time in pediatric cardiac surgery patients: A subgroup analysis of a randomized controlled trial
Martin, S. M., Tucci, M., Spinella, P. C., Ducruet, T., Fergusson, D. A., Freed, D. H., Lacroix, J., Poirier, N., Sivarajan, V. B., Steiner, M. E., et al
JTCVS open. 2023;15:454-467
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Editor's Choice
Abstract
OBJECTIVE This study aimed to determine whether or not transfusion of fresh red blood cells (RBCs) reduced the incidence of new or progressive multiple organ dysfunction syndrome compared with standard-issue RBCs in pediatric patients undergoing cardiac surgery. METHODS Preplanned secondary analysis of the Age of Blood in Children in Pediatric Intensive Care Unit study, an international randomized controlled trial. This study included children enrolled in the Age of Blood in Children in Pediatric Intensive Care Unit trial and admitted to a pediatric intensive care unit after cardiac surgery with cardiopulmonary bypass. Patients were randomized to receive either fresh (stored ≤7 days) or standard-issue RBCs. The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured up to 28 days postrandomization or at pediatric intensive care unit discharge, or death. RESULTS One hundred seventy-eight patients (median age, 0.6 years; interquartile range, 0.3-2.6 years) were included with 89 patients randomized to the fresh RBCs group (median length of storage, 5 days; interquartile range, 4-6 days) and 89 to the standard-issue RBCs group (median length of storage, 18 days; interquartile range, 13-22 days). There were no statistically significant differences in new or progressive multiple organ dysfunction syndrome between fresh (43 out of 89 [48.3%]) and standard-issue RBCs groups (38 out of 88 [43.2%]), with a relative risk of 1.12 (95% CI, 0.81 to 1.54; P = .49) and an unadjusted absolute risk difference of 5.1% (95% CI, -9.5% to 19.8%; P = .49). CONCLUSIONS In neonates and children undergoing cardiac surgery with cardiopulmonary bypass, the use of fresh RBCs did not reduce the incidence of new or progressive multiple organ dysfunction syndrome compared with the standard-issue RBCs. A larger trial is needed to confirm these results.
PICO Summary
Population
Children admitted to a paediatric intensive care unit after cardiac surgery with cardiopulmonary bypass, enrolled in the Age of Blood in Children in Pediatric Intensive Care Unit trial (ABC-PICU), (n= 178).
Intervention
Fresh (stored ≤7 days) red blood cells (RBCs), (n= 89).
Comparison
Standard-issue RBCs (n= 89).
Outcome
The authors performed a preplanned subgroup analysis of the ABC-PICU trial. The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured up to 28 days post-randomization or at paediatric intensive care unit discharge, or death. There were no statistically significant differences in new or progressive multiple organ dysfunction syndrome between fresh (43 out of 89 [48.3%]) and standard-issue RBCs groups (38 out of 88 [43.2%]), with a relative risk of 1.12; 95% CI [0.81, 1.54] and an unadjusted absolute risk difference of 5.1%; 95% CI [-9.5%, 19.8%].
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Effects of delayed cord clamping at different time intervals in late preterm and term neonates: a randomized controlled trial
Chaudhary, P., Priyadarshi, M., Singh, P., Chaurasia, S., Chaturvedi, J., Basu, S.
European journal of pediatrics. 2023;:1-11
Abstract
Delayed cord clamping (DCC) at delivery has well-recognized benefits; however, current scientific guidelines lack uniformity in its definition. This parallel-group, three-arm assessor-blinded randomized controlled trial compared the effects of three different timings of DCC at 30, 60, and 120 s on venous hematocrit and serum ferritin levels in late preterm and term neonates not requiring resuscitation. Eligible newborns (n = 204) were randomized to DCC 30 (n = 65), DCC 60 (n = 70), and DCC 120 (n = 69) groups immediately after delivery. The primary outcome variable was venous hematocrit at 24 ± 2 h. Secondary outcome variables were respiratory support, axillary temperature, vital parameters, incidences of polycythemia, neonatal hyperbilirubinemia (NNH), need and duration of phototherapy, and postpartum hemorrhage (PPH). Additionally, serum ferritin levels, the incidence of iron deficiency, exclusive breastfeeding (EBF) rate, and anthropometric parameters were assessed during post-discharge follow-up at 12 ± 2 weeks. Over one-third of the included mothers were anemic. DCC 120 was associated with a significant increase in the mean hematocrit by 2%, incidence of polycythemia, and duration of phototherapy, compared to DCC30 and DCC60; though the incidence of NNH and need for phototherapy was similar. No other serious neonatal or maternal adverse events including PPH were observed. No significant difference was documented in serum ferritin, incidences of iron deficiency, and growth parameters at 3 months even in the presence of a high EBF rate. Conclusion: The standard recommendation of DCC at 30-60 s may be considered a safe and effective intervention in the busy settings of low-middle-income countries with a high prevalence of maternal anemia. Trial registration: Clinical trial registry of India (CTRI/2021/10/037070). What is Known: • The benefits of delayed cord clamping (DCC) makes it an increasingly well-accepted practice in the delivery room. • However, uncertainty continues regarding the optimal timing of clamping; this may be of concern both in the neonate and the mother. What is New: • DCC at 120 s led to higher hematocrit, polycythemia and longer duration of phototherapy, without any difference in serum ferritin, and incidence of iron deficiency. • DCC at 30-60 s may be considered a safe and effective intervention in LMICs.
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Compliance and clinical benefit of deferasirox granule and dispersible tablet formulation in pediatric patients with transfusional iron overload: in a randomized, open-label, multicenter, phase II study
Taher, A. T., Wali, Y., Cruz, M. C., Charoenkwan, P., Aydinok, Y., Werner, O., Govindaraju, S., Romen, F., Viprakasit, V.
Haematologica. 2023
Abstract
CALYPSO (NCT02435212), a randomized, open-label, multicenter, phase 2 study evaluated the compliance, clinical benefits, and safety of deferasirox granules and dispersible tablets in pediatric patients with iron overload. Iron chelation therapy-naive and iron chelation therapy-pre-treated patients aged 2 to 0.5 mg/mg; 24.5% and 34.2%), upper respiratory tract infection (28.2% and 29.7%), and pyrexia (26.4% and 23.4%). In iron chelation therapy-naive patients, mean compliance and change from baseline in serum ferritin with both deferasirox formulations were not significantly different. The safety profile was comparable between granule and dispersible tablets formulations, and was consistent with the general safety profile of deferasirox.
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Methylprednisolone versus intravenous immunoglobulins in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): an open-label, multicentre, randomised trial
Welzel T, Atkinson A, Schöbi N, Andre MC, Bailey DGN, Blanchard-Rohner G, Buettcher M, Grazioli S, Koehler H, Perez MH, et al
The Lancet. Child & adolescent health. 2023
Abstract
BACKGROUND The emergence of paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) led to the widespread use of anti-inflammatory treatments in the absence of evidence from randomised controlled trials (RCTs). We aimed to assess the effectiveness of intravenous methylprednisolone compared with intravenous immunoglobulins. METHODS This is an open-label, multicentre, two-arm RCT done at ten hospitals in Switzerland in children younger than 18 years hospitalised with PIMS-TS (defined as age <18 years; fever and biochemical evidence of inflammation, and single or multiorgan dysfunction; microbiologically proven or putative contact with SARS-CoV-2; and exclusion of any other probable disease). Patients were randomly assigned 1:1 to intravenous methylprednisolone (10 mg/kg per day for 3 days) or intravenous immunoglobulins (2 g/kg as a single dose). The primary outcome was length of hospital stay censored at day 28, death, or discharge. Secondary outcomes included proportion and duration of organ support. Analyses were done by intention-to-treat. The study was registered with Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588). FINDINGS Between May 21, 2021, and April 15, 2022, 75 patients with a median age of 9·1 years (IQR 6·2-12·2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulins group). The median length of hospital stay was 6·0 days (IQR 4·0-8·0) in the methylprednisolone group and 6·0 days (IQR 5·0-8·8) in the intravenous immunoglobulins group (estimated effect size -0·037 of the log(10) transformed times, 95% CI -0·13 to 0·065, p=0·42). Fewer patients in the methylprednisolone group (ten [27%] of 37) required respiratory support compared with the intravenous immunoglobulin group (21 [55%] of 38, p=0·025). Need and duration of inotropes, admission to intensive care units, cardiac events after baseline, and major bleeding and thrombotic events were not significantly different between the study groups. INTERPRETATION In this RCT, treatment with methylprednisolone in children with PIMS-TS did not significantly affect the length of hospital stay compared with intravenous immunoglobulins. Intravenous methylprednisolone could be an acceptable first-line treatment in children with PIMS-TS. FUNDING NOMIS Foundation, Vontobel Foundation, and Gaydoul Foundation.
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Two-year outcomes following a randomised platelet transfusion trial in preterm infants
Moore CM, D'Amore A, Fustolo-Gunnink S, Hudson C, Newton A, Santamaria BL, Deary A, Hodge R, Hopkins V, Mora A, et al
Archives of disease in childhood. Fetal and neonatal edition. 2023
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Editor's Choice
Abstract
OBJECTIVE Assess mortality and neurodevelopmental outcomes at 2 years of corrected age in children who participated in the PlaNeT-2/MATISSE (Platelets for Neonatal Transfusion - 2/Management of Thrombocytopenia in Special Subgroup) study, which reported that a higher platelet transfusion threshold was associated with significantly increased mortality or major bleeding compared to a lower one. DESIGN Randomised clinical trial, enrolling from June 2011 to August 2017. Follow-up was complete by January 2020. Caregivers were not blinded; however, outcome assessors were blinded to treatment group. SETTING 43 level II/III/IV neonatal intensive care units (NICUs) across UK, Netherlands and Ireland. PATIENTS 660 infants born at less than 34 weeks' gestation with platelet counts less than 50×10(9)/L. INTERVENTIONS Infants were randomised to undergo a platelet transfusion at platelet count thresholds of 50×10(9)/L (higher threshold group) or 25×10(9)/L (lower threshold group). MAIN OUTCOMES MEASURES Our prespecified long-term follow-up outcome was a composite of death or neurodevelopmental impairment (developmental delay, cerebral palsy, seizure disorder, profound hearing or vision loss) at 2 years of corrected age. RESULTS Follow-up data were available for 601 of 653 (92%) eligible participants. Of the 296 infants assigned to the higher threshold group, 147 (50%) died or survived with neurodevelopmental impairment, as compared with 120 (39%) of 305 infants assigned to the lower threshold group (OR 1.54, 95% CI 1.09 to 2.17, p=0.017). CONCLUSIONS Infants randomised to a higher platelet transfusion threshold of 50×10(9)/L compared with 25×10(9)/L had a higher rate of death or significant neurodevelopmental impairment at a corrected age of 2 years. This further supports evidence of harm caused by high prophylactic platelet transfusion thresholds in preterm infants. TRIAL REGISTRATION NUMBER ISRCTN87736839.
PICO Summary
Population
Preterm infants enrolled in the PlaNeT-2/MATISSE trial, at 43 neonatal intensive care units across UK, Netherlands and Ireland (n= 660).
Intervention
Higher platelet transfusion threshold (n= 296).
Comparison
Lower platelet transfusion threshold (n= 305).
Outcome
The prespecified long-term follow-up outcome was a composite of death or neurodevelopmental impairment (developmental delay, cerebral palsy, seizure disorder, profound hearing or vision loss) at 2 years of corrected age. Follow-up data were available for 601 of 653 (92%) eligible participants. Of the 296 infants assigned to the higher threshold group, 147 (50%) died or survived with neurodevelopmental impairment, as compared with 120 (39%) of 305 infants assigned to the lower threshold group (OR: 1.54; 95% CI [1.09, 2.17]).