Liberal Versus Restrictive Platelet Transfusion for Treatment of Hemodynamically Significant Patent Ductus Arteriosus in Thrombocytopenic Preterm Neonates- A Randomized Open Label, Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Time to closure of PDA post randomization
研究概览
简要总结
Patent ductus arteriosus (PDA) is a common problem in preterm babies. Recently there have been various studies for and against an association between thrombocytopenia and PDA. A meta-analysis published in 2015 showed a marginally significant positive association between PDA and thrombocytopenia but these were all observational studies and there are no randomized controlled trials (RCT) on it. The investigators decided to conduct an RCT to determine whether liberal platelet transfusion criteria achieve earlier PDA closure rates than standard restrictive platelet transfusion criteria among thrombocytopenic preterm neonates (<35 weeks' gestation) with hemodynamically significant PDA presenting within the first 14 days of life. The investigators primary objective is to determine whether liberal platelet transfusion criteria achieve earlier PDA closure rates within 120 hours compared to standard restrictive platelet transfusion criteria among thrombocytopenic preterm neonates (<35 weeks' gestation) with hemodynamically significant PDA presenting within the first 14 days of life.
The investigators will stratify the study population based on platelet count, i.e < 50000 and 50000-100000 per microlitre, and will randomly allocate participants to control and intervention group. Babies in the intervention group will receive platelet transfusion to maintain the platelet count above 100,000 per microlitre. Babies in control group will receive platelets only when clinically indicated and as per current standard indications. The investigators will perform an echocardiogram at baseline to document a hemodynamically significant PDA (hsPDA) and then serially to look for the closure of PDA. Medical management of PDA will be as per unit policy. The investigators will follow the baby till PDA closes or 120 hours post randomization.
详细描述
Study Background:
Preterm babies are a unique group of patients in Newborn Intensive Care Unit. Patent ductus arteriosus (PDA) is a common complication related to the gestational age of preterm birth. In infants born at less than 32 weeks of gestation, the frequency of PDA has been reported from 50% to 80%. Physiologic ductus arteriosus closure occurs in the first 3 days after birth. The persistence of a PDA beyond the first postnatal days of life, however, is frequently associated with multiple severe complications, predominantly in the most immature infants It is currently believed that ductus arteriosus (DA) closure involves a two-step process. The first, 'provisional' closure is accomplished by smooth muscle cell contraction and ductus arteriosus (DA) constriction. Subsequently, the proliferation of cells within the former DA lumen leads to anatomical remodeling of the DA and permits permanent closure. Recently an association between the absolute platelet count and the closure of ductus arteriosus has been the focus of research. Various prospective and retrospective studies have been conducted for the same. In 2015 systematic review and meta-analysis by Sorina et al showed a significant positive association between PDA and thrombocytopenia. Hence the investigators planned randomized controlled trial to look for the effect of platelet transfusion on closure rates of ductus arteriosus.
Research question:
Do liberal platelet transfusion criteria achieve earlier PDA closure rates than standard restrictive platelet transfusion criteria among thrombocytopenic preterm neonates (<35 weeks gestation) with hemodynamically significant PDA presenting within the first 14 days of life?
Objectives:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Day 至 14 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Gestational age up to 34 6/7 weeks
- •PDA detected for the first time at less than 14 days of postnatal age
- •Clinically and/or echocardiographically hemodynamically significant PDA Note: ELBW neonates will be screened in first 48 hours as per unit policy; the rest will undergo echocardiography only when there are clinical signs of PDA.
- •Platelet count within 24 hours prior to inclusion is less than 100,000 per microliter.
- •Note: If a platelet count is already available within 24 hours prior to inclusion it will be accepted as a valid platelet count. If not, an urgent absolute platelet count will be performed.
排除标准
- •Echocardiographically proven structural congenital heart disease.
- •Major life-threatening malformation
- •Received platelet concentrate between the last available platelet count and the point of randomisation
研究组 & 干预措施
Liberal Platelet transfusion group
Platelet transfusion to maintain a platelet count above 1,00,000 per microliter until one of the endpoints is met.
As all subjects recruited in the trial will have hemodynamically significant (hs) PDA, they will all be medically treated as per standard of care. Treatment regimens will be as follows, depending on the discretion of the treating physician:
Ibuprofen:
Dosage-10 mg/kg stat followed by 5 mg/kg/dose x 2 doses at 24 hours intervals Route- oral
Paracetamol:
Dosage-15 mg/kg/dose every 6 hourly x 12 doses Route - IV
干预措施: Liberal platelet transfusion (Biological)
Liberal Platelet transfusion group
Platelet transfusion to maintain a platelet count above 1,00,000 per microliter until one of the endpoints is met.
As all subjects recruited in the trial will have hemodynamically significant (hs) PDA, they will all be medically treated as per standard of care. Treatment regimens will be as follows, depending on the discretion of the treating physician:
Ibuprofen:
Dosage-10 mg/kg stat followed by 5 mg/kg/dose x 2 doses at 24 hours intervals Route- oral
Paracetamol:
Dosage-15 mg/kg/dose every 6 hourly x 12 doses Route - IV
干预措施: Paracetamol (Drug)
Liberal Platelet transfusion group
Platelet transfusion to maintain a platelet count above 1,00,000 per microliter until one of the endpoints is met.
As all subjects recruited in the trial will have hemodynamically significant (hs) PDA, they will all be medically treated as per standard of care. Treatment regimens will be as follows, depending on the discretion of the treating physician:
Ibuprofen:
Dosage-10 mg/kg stat followed by 5 mg/kg/dose x 2 doses at 24 hours intervals Route- oral
Paracetamol:
Dosage-15 mg/kg/dose every 6 hourly x 12 doses Route - IV
干预措施: Ibuprofen (Drug)
Restrictive platelet transfusion group
Platelet transfusion for standard criteria.
As all subjects recruited in the trial will have hemodynamically significant (hs) PDA, they will all be medically treated as per standard of care. Treatment regimens will be as follows, depending on the discretion of the treating physician:
Ibuprofen:
Dosage-10 mg/kg stat followed by 5 mg/kg/dose x 2 doses at 24 hours intervals Route- oral
Paracetamol:
Dosage-15 mg/kg/dose every 6 hourly x 12 doses Route - IV
干预措施: Restrictive platelet transfusion (Biological)
Restrictive platelet transfusion group
Platelet transfusion for standard criteria.
As all subjects recruited in the trial will have hemodynamically significant (hs) PDA, they will all be medically treated as per standard of care. Treatment regimens will be as follows, depending on the discretion of the treating physician:
Ibuprofen:
Dosage-10 mg/kg stat followed by 5 mg/kg/dose x 2 doses at 24 hours intervals Route- oral
Paracetamol:
Dosage-15 mg/kg/dose every 6 hourly x 12 doses Route - IV
干预措施: Paracetamol (Drug)
Restrictive platelet transfusion group
Platelet transfusion for standard criteria.
As all subjects recruited in the trial will have hemodynamically significant (hs) PDA, they will all be medically treated as per standard of care. Treatment regimens will be as follows, depending on the discretion of the treating physician:
Ibuprofen:
Dosage-10 mg/kg stat followed by 5 mg/kg/dose x 2 doses at 24 hours intervals Route- oral
Paracetamol:
Dosage-15 mg/kg/dose every 6 hourly x 12 doses Route - IV
干预措施: Ibuprofen (Drug)
结局指标
主要结局
Time to closure of PDA post randomization
时间窗: within 120 hours post randomisation
Time point at which closure (Absence of flow in PDA on colour doppler) is documented first time will be considered as time to closure of PDA
次要结局
- Proportion of participants in whom PDA is echocardiographically hemodynamically significant(at 120 hours after randomization)
- Cumulative volume of platelet concentrate received(within 120 hours after randomization)
- Reopening rate of PDA that had initially closed(within 120 hours of randomization)
- New onset IVH of any grade(within 120 hours after randomization)
- New onset IVH of grade 3or 4(within 120 hours after randomization)
- Duration of hospital stay(All subjects will be part of the study until death or discharge from the hospital.Timeframe for measuring duration of hospital stay is from the point of randomisation through the study period which will be approximately upto 30 days post randomisation)
- Mortality(All subjects will be part of the study until death or discharge from the hospital. Timeframe for measuring mortality as an outcome is from the point of randomisation through the study period which will be approximately upto 30 days post randomisation)
- Proportion of participants in whom PDA is open(at 120 hours after randomization)
- Number of participants with Clinical bleed of any kind ( defined below)(within 120 hours after randomization)
研究者
Sourabh Dutta
Dr
Post Graduate Institute of Medical Education and Research, Chandigarh