Jahr Jonathan S, Mackenzie Colin, Pearce L Bruce, Pitman Arkadiy, Greenburg A Gerson
David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
J Trauma. 2008 Jun;64(6):1484-97. doi: 10.1097/TA.0b013e318173a93f.
The ability of hemoglobin based oxygen carrier-201 (HBOC-201) to safely reduce and/or eliminate perioperative transfusion was studied in orthopedic surgery patients.
A randomized, single-blind, packed red blood cell (PRBC)-controlled, parallel-group multicenter study was conducted. Six hundred eighty-eight patients were randomized to treatment with HBOC-201 (H, n = 350) or PRBC (R, n = 338) at the first transfusion decision. Primary endpoints were transfusion avoidance and blinded assessment [Mann-Whitney estimator (MW)] of safety noninferiority. Groups were compared directly and by paired/matching group analyses predicated on a prospectively defined dichotomy [treatment success (HH) vs. failure (HR)] in the H arm and an equivalently defined dichotomy [</=3 (R3-) vs. >3 (R3+) units PRBC] in the R arm, based on need (moderate vs. high) for additional oxygen carrying capacity.
A total of 59.4% of patients in the H arm avoided PRBC transfusion. Adverse events (8.47 vs. 5.88), and serious adverse events (SAEs) (0.35 vs. 0.25) per patient were higher in the H versus R arms (p < 0.001 and p < 0.01) with MW = 0.561 (95 CI 0.528-0.594). HH versus R3- had identical (0.14) serious adverse events/patient and a MW = 0.519 (95% confidence limit 0.481-0.558), whereas the incidence was higher (0.63 vs. 0.47) for HR versus R3+ with a MW = 0.605 (95% confidence limit 0.550-0.662). Age (>80 years), volume overload and undertreatment contributed to this imbalance.
HBOC-201 eliminated transfusion in the majority of subjects. The between arms (H vs. R) safety analysis was unfavorable and likely related to patient age, volume overload, and undertreatment and was isolated to patients that could not be managed by HBOC-201 alone. However, patients <80 years old with moderate clinical need may safely avoid transfusion when treated with up to 10 units of HBOC-201.
在骨科手术患者中研究了基于血红蛋白的氧载体-201（HBOC-201）安全减少和/或消除围手术期输血的能力。
进行了一项随机、单盲、浓缩红细胞（PRBC）对照、平行组多中心研究。688例患者在首次输血决策时被随机分为接受HBOC-201治疗组（H组，n = 350）或PRBC治疗组（R组，n = 338）。主要终点是避免输血以及对安全性非劣效性的盲法评估[曼-惠特尼估计值（MW）]。根据H组中预先定义的二分法[治疗成功（HH）与失败（HR）]以及R组中基于对额外携氧能力的需求（中度与高度）等效定义的二分法[≤3（R3-）与>3（R3+）单位PRBC]，直接比较两组并通过配对/匹配组分析进行比较。
H组中共有59.4%的患者避免了PRBC输血。H组与R组相比，每位患者的不良事件（8.47对5.88）和严重不良事件（SAEs）（0.35对0.25）更高（p < 0.001和p < 0.01），MW = 0.561（95%CI 0.528 - 0.594）。HH与R3-的严重不良事件/患者相同（0.14），MW = 0.519（95%置信区间0.481 - 0.558），而HR与R3+相比发生率更高（0.63对0.47），MW = 0.605（95%置信区间0.550 - 0.662）。年龄（>80岁）、容量超负荷和治疗不足导致了这种不平衡。
HBOC-201使大多数受试者避免了输血。组间（H组与R组）安全性分析结果不利，可能与患者年龄、容量超负荷和治疗不足有关，且仅限于不能仅用HBOC-201治疗的患者。然而，临床需求为中度的<80岁患者在接受多达10单位HBOC-201治疗时可安全避免输血。
