Sprague Sheila, Bzovsky Sofia, Connelly Daniel, Thabane Lehana, Adachi Jonathan D, Slobogean Gerard P
1Division of Orthopaedic Surgery, Department of Surgery, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4L8 Canada.
2Department of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4L8 Canada.
Pilot Feasibility Stud. 2019 Nov 22;5:135. doi: 10.1186/s40814-019-0524-4. eCollection 2019.
Observational studies have found that 75% of healthy adult fracture patients (ages 18-50) have serum 25-hydroxyvitamin D (25(OH)D) levels < 30 ng/mL. Although lower serum 25(OH)D levels have yet to be correlated to fracture healing complications or poor fracture outcomes, many orthopedic surgeons are routinely prescribing vitamin D supplements to improve fracture healing in healthy non-osteoporotic patients. To address this gap in the literature, we propose a phase II exploratory randomized controlled trial comparing three vitamin D dosing regimens for early surrogate treatment response.
We will conduct a 4-arm blinded exploratory phase II trial in 96 adults aged 18-50 years with a closed or low-grade open (Gustilo type I or II) tibial or femoral shaft fracture. Eligible patients will be randomized in equal allocation ratio of 1:1:1:1 to one of the treatment groups: (1) 150,000 IU loading dose vitamin D plus daily dose placebo; (2) loading dose placebo plus 4000 IU vitamin D per day, (3) loading dose placebo plus 600 IU vitamin D per day, or (4) loading dose placebo plus daily dose placebo. The primary outcome is fracture healing, assessed as follows: (1) clinical fracture healing measured using the Function IndeX for Trauma, (2) radiographic fracture healing measured using the Radiographic Union Score for Tibial fractures, and (3) biological fracture healing measured using serum levels of cross-linked C-terminal telopeptides of type I collagen and amino-terminal procollagen propeptides of collagen type I. The main secondary outcome will be assessed by measuring serum 25(OH)D levels. All outcome analyses will be exploratory and adhere to the intention-to-treat principle. Per-protocol sensitivity analyses will also be conducted.
Study results will be disseminated through a publication in an academic journal and presentations at orthopedic conferences. Study results will inform dose selection for a large definitive randomized controlled trial and provide preliminary clinical data on which dose may improve acute fracture healing outcomes in healthy adult patients (18-50 years) at 3 months.
Vita-Shock (A Blinded Exploratory Randomized Controlled Trial to Determine Optimal Vitamin D Supplementation Strategies for Acute Fracture Healing) was registered at ClinicalTrials.gov (identifier NCT02786498) prior to enrollment of participants.
观察性研究发现，75%的健康成年骨折患者（年龄在18至50岁之间）血清25-羟维生素D（25(OH)D）水平<30 ng/mL。尽管较低的血清25(OH)D水平尚未与骨折愈合并发症或不良骨折预后相关联，但许多骨科医生仍常规开具维生素D补充剂，以改善健康的非骨质疏松患者的骨折愈合情况。为填补文献中的这一空白，我们提出一项II期探索性随机对照试验，比较三种维生素D给药方案的早期替代治疗反应。
我们将对96名年龄在18至50岁之间、患有闭合性或低级别开放性（Gustilo I型或II型）胫骨干或股骨干骨折的成年人进行一项4组盲法探索性II期试验。符合条件的患者将按1:1:1:1的均等分配比例随机分为以下治疗组之一：（1）150,000 IU负荷剂量维生素D加每日剂量安慰剂；（2）负荷剂量安慰剂加每日4000 IU维生素D；（3）负荷剂量安慰剂加每日600 IU维生素D；或（4）负荷剂量安慰剂加每日剂量安慰剂。主要结局为骨折愈合，评估如下：（1）使用创伤功能指数测量临床骨折愈合情况；（2）使用胫骨骨折影像学愈合评分测量影像学骨折愈合情况；（3）使用I型胶原交联C末端肽和I型胶原氨基末端前胶原肽的血清水平测量生物学骨折愈合情况。主要次要结局将通过测量血清25(OH)D水平进行评估。所有结局分析均为探索性，并遵循意向性分析原则。还将进行符合方案敏感性分析。
研究结果将通过在学术期刊上发表以及在骨科会议上进行报告来传播。研究结果将为大型确定性随机对照试验的剂量选择提供依据，并提供初步临床数据，表明哪种剂量可能在3个月时改善健康成年患者（18至50岁）的急性骨折愈合结局。
Vita-Shock（一项确定急性骨折愈合最佳维生素D补充策略的盲法探索性随机对照试验）在招募参与者之前已在ClinicalTrials.gov注册（标识符NCT02786498）。
