Oral Peri-operative TIming of Metformin (or) Salsalate to Improve Non-cardiac Surgery Glucose Control - A Placebo-Controlled Internal Feasibility Trial
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Participants with hyperglycemia
研究概览
简要总结
Hypothesis: In surgical patients with type 2 diabetes, taking either metformin or salsalate on the morning of surgery will reduce the incidence of hyperglycemia, inflammation and even surgical site infections, without any obvious patient risk relative to patients given a placebo control.
Anesthesia and surgery induce a number of metabolic disturbances, particularly among patients with type 2 diabetes (T2D). This includes altered glucose metabolism and hyperglycemia, which is associated with significant morbidity and mortality, including an increase in surgical site infections (SSI). Although insulin protocols can reduce blood glucose levels in hyperglycemic surgical patients, leading to reduced SSI, this has caused severe hypoglycemia in a number of patients. Instead, the use of simple and effective interventions, such as continuing metformin on the day of surgery, could represent an important step toward reducing the incidence of these morbid outcomes while improving glucose control. Alternatively, salsalate, a non-acetylated dimer of salicylic acid, has also emerged as a novel glucose-lowering medication that also possesses important anti-pyretic and anti-inflammatory properties and could prove equally effective.These refinements may also reduce SSI and inflammation. If the proposed pilot trial, to continue metformin, or take salsalate, peri-operatively, is as safe and easy as the investigators anticipate it will allow for the planning of a future definitive randomized clinical trial. The aims of this pilot trial are to assess the feasibility of safely continuing metformin, or taking salsalate on the day of surgery, with the goal of reducing the incidence of hyperglycemic events. This includes assessing our ability to recruit patients, adhere to the proposed study protocol, assess workload,and measure the desired outcomes, all of which are crucial for the planning of a subsequent clinical trial.
详细描述
This internal pilot study (n=36) is designed as a 3-arm, parallel, placebo-controlled trial with block randomization. All parties will be blinded.
Patient Recruitment: Patients with T2D on metformin presenting to the Hamilton Health Sciences (HHS) preoperative clinic for elective surgery requiring general anesthetic will be screened for eligibility.
Sample Size: 36 patients over the 1-year study. This sample size will allow for 3 groups of 12, which permits block randomization and precise confidence interval (CI) calculations.
Randomization and Allocation: Patients will be randomized on the day of their pre-operative assessment by our department statistician using a computer-generated table, with an allocation ratio of 1:1:1 in random permuted blocks of 3 or 6. Only the pharmacist and statistician will know the allocation sequence. Concealed medications (over-encapsulated) will be provided to the RC upon confirming the allotment with a unique identification number (UIN), recorded on the patient-specific case record form (CRF).
Application of Intervention: Our intervention involves self-administered metformin (patient's usual dose) vs. salsalate (1.5g) vs. placebo with sips of water 2h prior to surgery. Baseline data (age, height, weight, ASA score, mean arterial BP, and baseline glucose) will be collected by the RC in the pre-operative assessment area, and flash glucose sensors (FreeStyle Libre, Abbot) will be placed on the upper arm as per manufacturer's instructions and readings collected by the RC. Study data will be securely stored in the anesthesia research office, McMaster University. Standard monitors will be used in the operating room, with any additional monitoring left to the anesthesiologist's discretion. Although most anesthetics appear to modify glucose metabolism, general anesthesia will be provided in their preferred manner (including dexamethasone administration for post-operative nausea and vomiting prophylaxis) to improve generalizability. Details of the type of drugs, fluids and blood loss will be recorded. Following surgery, patients will be brought to the PACU for routine monitoring (30-60 min), and additional blood samples will be drawn. Subsequent samples will be collected on the evening of surgery (6-12h) and POD1. Any episodes of hyper- or hypoglycemia will be managed routinely at the treating physician's discretion and details recorded.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Patients will be randomized on the day of their pre-operative assessment by our department statistician using a computer-generated table, with an allocation ratio of 1:1:1 in random permuted blocks of 3 or 6. Only the pharmacist and statistician will know the allocation sequence. Concealed medications (over-encapsulated) will be provided to the RC upon confirming the allotment with a unique identification number (UIN), recorded on the patient-specific case record form (CRF).
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Elective surgical patients requiring a general anesthetic at HHS requiring at least an overnight admission;
- •Using metformin regularly for control of T2D;
- •American Society of Anesthesiologists (ASA) physical classification I, II and III;
- •Less than 1000 mL of blood loss is expected.
排除标准
- •Procedures for which non-steroidal anti-inflammatory drugs are contraindicated;
- •Diagnosis of renal failure (estimated glomerular filtration rate <60 mL/min/1.73m2);
- •Liver failure;
- •Previous episodes of congestive heart failure;
- •Severe hypoglycemia in the past year;
- •Conditions masking hypoglycemia (e.g. autonomic neuropathy);
- •Low random blood glucose during pre-screening (≤4.0 mmol/L);
- •Received contrast within 48h prior to, or during, surgery.
研究组 & 干预措施
Metformin
Self-administered metformin (patient's usual dose) taken 2 hours prior to surgery
干预措施: Metformin (Drug)
Salsalate
Self-administered salsalate taken 2 hours prior to surgery
干预措施: Salsalate (Drug)
Placebo
Self-administered placebo taken 2 hours prior to surgery
结局指标
主要结局
Participants with hyperglycemia
时间窗: One year
Detect change in hyperglycemic events (glucose \>11mmol/L) at the 4 blood sampling time points for each participant
Feasibility: recruitment rate (percentage)
时间窗: One year
Percentage (%) of individuals who were approached in the pre-operative clinic that enrolled in the study
Feasibility: recruitment rate (total number per month)
时间窗: One year
Number (n) of individuals recruited each month
次要结局
- Blood glucose levels (glycemic control)(One year)
- Number of participants with inflammation(One year)