Protection of the Heart With Doxycycline During Coronary Artery Bypass Grafting: A Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Left Ventricular Stroke Work Index (LVSWI)
研究概览
简要总结
The purpose of this study is to determine whether doxycycline (Periostat) at a sub-antimicrobial dose will decrease reperfusion injury after coronary artery bypass grafting (CABG) surgery with cardiopulmonary bypass (CPB).
详细描述
This proposal is for a randomized, placebo-controlled, double-blinded study of the use of doxycycline in patients requiring CABG surgery. Patients will be randomized 1:1 to receive either doxycycline or placebo.
This study will be conducted in a blinded manner. The pharmacy will randomize patients and will have the randomization code. The code will only be broken in the case of an emergency and the event will be fully documented.
In addition to standard care, patients will receive oral administration of 20 mg of doxycycline or placebo twice a day at least 2 days prior to surgery, on the day of surgery, and on postoperative days 1, 2, and 3.
Myocardial atrial biopsies will be taken at 2 time points during the CABG procedure: during cannulation of the right atrium and 10 minutes after cross-clamp release. Tissue will be analyzed for MMP-2 and -9 activity and TnI and MLC-1 levels.
A Swan-Ganz-Catheter will be placed in the pulmonary artery over 24 hours to measure hemodynamics (LVSWI).
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Aged 18 through 80 years, inclusive
- •Scheduled for primary CABG surgery with CPB
排除标准
- •Females of childbearing potential
- •Emergency CABG
- •Previous sternotomy
- •Planned simultaneous surgery (i.e. valve repair or carotid endarterectomy)
- •Myocardial infarction within 48 hours
- •Pre-operative atrial fibrillation
- •Pre-operative ventricular pacing or left bundle branch block (LBBB)
- •Known hypersensitivity to tetracycline class antibiotics
- •Renal failure requiring dialysis
研究组 & 干预措施
Placebo oral tablet
Patients received oral administration of matching placebo pills, twice a day at least 2 days prior to surgery, on the day of surgery, and for the first 3 postoperative days (via a nasogastric tube or orally when patients tolerated it).
干预措施: Placebo Oral Tablet (Drug)
Periostat
Patients received oral administration of 20 mg of doxycycline, twice a day at least 2 days prior to surgery, on the day of surgery, and for the first 3 postoperative days (via a nasogastric tube or orally when patients tolerated it).
干预措施: Periostat (Drug)
结局指标
主要结局
Left Ventricular Stroke Work Index (LVSWI)
时间窗: Before surgery up to 24h of reperfusion
Measure of global left ventricular function. The formula used for calculation is: LVSWI= SI x MAP x 0.0144 LVSWI = Left Ventricular Stroke Work Index (g\*m/m2) SI = Stroke Index (mL/beat/m2) MAP = Mean Arterial Pressure (mmHg) 0.0144 is a conversion term to equalize units.
次要结局
- Cleaved TroponinI/GAPDH Ratios in Right Atrial Biopsy(Before surgery and 10 minutes reperfusion after surgery)
- Venous Plasma Concentration of C-reactive Protein(Before surgery and up to 72 h reperfusion after surgery)
- Cardiac Matrix Metalloproteinase-9 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion(Before surgery and 10 minutes reperfusion after surgery)
- Cardiac Matrix Metalloproteinase-2 Activity in Right Atrial Biopsies at 10 Minutes Reperfusion(Before surgery and 10 minutes reperfusion after surgery)
- Venous Plasma Concentration of IL-6(Before surgery and up to 72 h reperfusion after surgery)
- Venous Plasma Cardiac Matrix Metalloproteinase-2 Activity Before and After Reperfusion(Before surgery and up to 72 h reperfusion after surgery)
- Venous Plasma Cardiac Matrix Metalloproteinase-9 Activity Before and After Reperfusion(Before surgery and up to 72 h reperfusion after surgery)
- Venous Plasma Concentration of Troponin-I(Before surgery and 10 minutes reperfusion after surgery)
研究者
Barry Finegan
Professor
University of Alberta