The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture
The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture
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DOI：
10.1111/j.1532-5415.2004.52156.x
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发表时间：
2004-04-01
影响因子：
6.3
通讯作者：
Fuh, V
中科院分区：
文献类型：
--
作者：
Bach, MA;Rockwood, K;Fuh, V
目的：为了评估MK-0677，一种口服活性生长激素（GH）促分泌剂，对以前移动的老年人髋部骨折功能恢复的影响，设计：安慰剂对照，随机，双盲试验，设置：在英国，瑞典，丹麦，比利时，瑞士，加拿大和美国的13个医疗中心。患者在术后3 - 14天或骨折后不超过18天在急诊医院和康复中心招募。入选标准包括年龄在65岁及以上、骨折前能走动、术后病情稳定、精神正常的髋部骨折患者。如果患者患有多发性骨折或严重创伤、糖尿病、癌症、不受控制的高血压、充血性心力衰竭或参与肢端的全髋关节置换术，则将其排除在外。干预：随机分配至MK-0677或安慰剂每日治疗6个月。患者在完成治疗后再随访6个月。测量：从第6周到第26周的功能性能指标的变化。其他结果测量包括疗养院疾病影响概况（SIP-NH）的变化、独立生活的能力和胰岛素样生长因子I（IGF-I）levels.Results：MK-0677治疗使血清IGF-I水平增加84%（95%置信区间（CI）=63-107），而安慰剂增加17%（95%CI =8-28）。MK-0677与安慰剂之间在功能性能指标或总体SIP-NH评分改善方面无显著差异。虽然MK-0677患者表现出更大的改善相对于安慰剂在三个四下肢功能的性能指标，在物理领域的SIP，并在独立生活的能力，这些差异并不具有统计学意义。在临床试验中测量髋部骨折患者的功能是困难的，因为缺乏有效的结果测量，高变异性，缺乏基线评估。目前的功能性能指标可能不足以作为小型干预研究的主要终点;或者，刺激GH可能不会导致显著的功能改善。
Objectives: To evaluate the effects of MK-0677, an orally active growth hormone (GH) secretagogue, on functional recovery from hip fracture in previously mobile older individuals.Design: Placebo-controlled, randomized, double-blind trial.Setting: Thirteen medical centers in England, Sweden, Denmark, Belgium, Switzerland, Canada, and the United States. Patients were recruited between 3 and 14 days postoperatively, or no more than 18 days postfracture, at acute care hospitals and rehabilitation centers.Participants: One hundred sixty-one hip-fracture patients were enrolled. Entry criteria included consenting hip-fracture patients who were aged 65 and older and who were ambulatory before their fracture, medically stable postoperatively, and mentally competent. Patients were excluded if they had multiple fractures or severe trauma, diabetes mellitus, cancer, uncontrolled hypertension, congestive heart failure, or total hip replacement in the involved extremity.Intervention: Random assignment to 6 months of daily treatment with MK-0677 or placebo. Patients were followed for an additional 6 months after completion of therapy.Measurements: Change from Week 6 to Week 26 in a panel of functional performance measures. Additional outcome measures included change in the Sickness Impact Profile for Nursing Homes (SIP-NH), the ability to live independently, and insulin-like growth factor I (IGF-I) levels.Results: MK-0677 treatment increased serum IGF-I levels by 84% (95% confidence interval (CI)=63-107), compared with an increase of 17% (95% CI=8-28) on placebo. There were no significant differences between MK-0677 and placebo in improvement in functional performance measures or in the overall SIP-NH score. Although MK-0677 patients showed greater improvement relative to placebo in three of four lower extremity functional performance measures, in the physical domain of the SIP, and in the ability to live independently, these differences were not statistically significant.Conclusion: Although MK-0677 treatment increased serum IGF-I, it is uncertain whether clinically significant effects on physical function were achieved. Measuring function in clinical trials in hip-fracture patients is difficult because of the lack of validated outcome measures, high variability, and the lack of a baseline assessment. Present functional performance measures may not be sufficiently responsive for use as the primary endpoint of small intervention studies; alternatively, stimulation of GH may not result in significant functional improvement.