Granulocyte-macrophage colony stimulating factor administered as prophylaxis for reduction of sepsis in extremely preterm, small for gestational age neonates (the PROGRAMS trial): a single-blind, multicentre, randomised controlled trial
Granulocyte-macrophage colony stimulating factor administered as prophylaxis for reduction of sepsis in extremely preterm, small for gestational age neonates (the PROGRAMS trial): a single-blind, multicentre, randomised controlled trial
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DOI：
10.1016/s0140-6736(09)60071-4
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发表时间：
2009-01-17
期刊：
影响因子：
168.9
通讯作者：
Modi, Neeno
中科院分区：
文献类型：
--
作者：
Carr, Robert;Brocklehurst, Peter;Modi, Neeno
背景全身性败血症是早产儿死亡的主要原因。有令人信服的理论原因，造血集落刺激因子治疗可能会减少败血症和改善结果，因此这些药物已进入新生儿医学的使用没有足够的证据。我们评估是否粒细胞-巨噬细胞集落刺激因子（GM-CSF）作为预防早产儿，新生儿在高风险的中性粒细胞减少症将减少败血症，死亡率和morbidity.Methods我们进行了单盲，多中心，随机对照试验，2000年6月至2006年6月在26个中心。280例小于或等于31周妊娠且出生体重低于第10百分位数的新生儿在出生后72小时内随机接受GM-CSF 10 pg/kg/天皮下注射，持续5天或标准管理。从招募到第28天，由治疗临床医生填写详细的每日临床记录表。主要结局是从试验开始到14天的无败血症生存期。本研究注册为国际标准随机对照试验，编号ISRCTN 42553489。研究结果：在试验开始后的前11天内，接受GM-CSF治疗的婴儿的中性粒细胞计数比对照组婴儿显著上升更快（中性粒细胞计数斜率差异为0.34x10（9）/L/d; 95%CI为0.001）。12-0.56）。所有婴儿的无败血症存活率无显著差异（139例治疗婴儿中有93例，141例对照婴儿中有105例;差异-8%，95%CI-18至3）。本试验和以前发表的预防性试验的荟萃分析显示，没有生存benefit.Interpretation早期产后预防性GM-CSF纠正中性粒细胞减少症，但不减少败血症或改善生存和极早产儿的短期结局。
Background Systemic sepsis is a major cause of death in preterm neonates. There are compelling theoretical reasons why treatment with haemopoietic colony-stimulating factors might reduce sepsis and improve outcomes, and as a consequence these agents have entered into use in neonatal medicine without adequate evidence. We assessed whether granulocyte-macrophage colony stimulating factor (GM-CSF) administered as prophylaxis to preterm, neonates at high risk of neutropenia would reduce sepsis, mortality, and morbidity.Methods We undertook a single-blind, multicentre, randomised controlled trial in 26 centres between June, 2000, and June, 2006. 280 neonates of below or equal to 31 weeks' gestation and below the 10th centile for birthweight were randomised within 72 h of birth to receive GM-CSF 10 pg/kg per day subcutaneously for 5 days or standard management. From recruitment to day 28 a detailed daily clinical record form was completed by the treating clinicians. Primary outcome was sepsis-free survival to 14 days from trial entry. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN42553489.Findings Neutrophil counts after trial entry rose significantly more rapidly in infants treated with GM-CSF than in control infants during the first 11 days (difference between neutrophil count slopes 0.34x10(9)/L/day; 95% CI 0 . 12-0.56). There was no significant difference in sepsis-firee survival for all infants (93 of 139 treated infants, 105 of 141 control infants; difference -8%, 95% Cl -18 to 3). A meta-analysis of this trial and previous published prophylactic trials showed no survival benefit.Interpretation Early postnatal prophylactic GM-CSF corrects neutropenia but does not reduce sepsis or improve survival and short-term outcomes in extremely preterm neonates.Funding Action Medical Research.