Calcium Chloride for Prevention of Blood Loss From Uterine Atony During Intrapartum Cesarean Delivery (CALBLOC): a Double Blind, Randomized, Placebo Controlled Trial and Nested Population Pharmacokinetic and Pharmacodynamic Analysis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Quantitative Blood Loss
研究概览
简要总结
Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity and mortality worldwide. Up to 80% of PPH is caused by uterine atony, the failure of the uterine smooth muscle to contract and compress the uterine vasculature after delivery. Laboratory and epidemiological studies show that low extracellular and serum calcium levels, respectively, decrease uterine contractility. A pilot study performed by the investigators supports the hypothesis that intravenous calcium chloride is well tolerated and may have utility in preventing uterine atony. The proposed research will establish the relationship between uterine tone and calcium through a clinical trial with an incorporated pharmacokinetic and pharmacodynamic (PK/PD) study. In a randomized, placebo-controlled, double-blind trial, investigators will establish the effect of 1 gram of intravenous calcium chloride upon quantitative blood loss and uterine tone during cesarean delivery in parturients with high risk of uterine atony. Investigators will concurrently collect serial venous blood samples to measure calcium for PK/PD modeling in this pregnant study cohort. High-quality clinical research and development of novel therapeutics to manage uterine atony are critical to reduce the high maternal morbidity and mortality from PPH.
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
The patient, obstetrician, anesthesiologist, and clinical research staff will be blinded to the intervention. Drugs will be labeled only as "study drug"
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patient had a trial of labor for vaginal delivery prior to cesarean
- •Patient received an oxytocin infusion for labor augmentation or induction prior to cesarean
排除标准
- •renal dysfunction with serum Cr >1.0 mg/dL
- •known underlying cardiac condition
- •treatment with digoxin within the last 2 weeks for a maternal or fetal indication
- •treatment with a calcium channel blocker medication within 24 hours
- •hypertension necessitating intravenous antihypertensive medication within 24 hours
- •emergent case in which study participation could in any way impede patient care by the judgement of the obstetrician, anesthesiologist, or bedside nurse
研究组 & 干预措施
Calcium chloride
1 gram of calcium chloride in total volume 60mL with sterile saline, delivered over 10 minute controlled infusion at a constant rate (360mL/hour) beginning 2 minutes after fetal delivery and 1 minute after delayed cord clamp.
This intervention occurs IN ADDITION TO standard care with oxytocin 2 unit bolus and infusion at 7.5 units per hour which begins immediately after fetal delivery.
干预措施: Calcium chloride (Drug)
Saline placebo
60mL sterile saline, delivered over 10 minute controlled infusion at a constant rate (360mL/hour) beginning 2 minutes after fetal delivery and 1 minute after delayed cord clamp.
This intervention occurs IN ADDITION TO standard care with oxytocin 2 unit bolus and infusion at 7.5 units per hour which begins immediately after fetal delivery.
干预措施: Saline placebo (Drug)
结局指标
主要结局
Quantitative Blood Loss
时间窗: measurement occurs at conclusion of operating room case
Standardized volumetric and gravimetric assessment of blood loss during cesarean. Note: will analyze all participants, but planned subgroup analysis will also occur excluding patients with non-atonic reasons for blood loss including hysterotomy extension, placental abruption, cervical or vaginal laceration, etc
次要结局
- Number of Participants With Postpartum Hemorrhage(operative course (within 4-6 hours of fetal delivery))
- Number of Participants With Second Line Uterotonic Requirement(within 4 hours of delivery)
- Fluid Requirement(Operating room duration, usually 2 hours)
- Pharmacokinetics of Calcium Chloride - Baseline Ionized Calcium(In the operating room prior to study drug administration (generally <30 minutes prior to fetal delivery and study drug administration))
- Number of Patients With a Transfusion Requirement(96 hours of delivery)
- Change in Hematocrit From Baseline(1 day)
- Total Oxytocin Bolus Requirement(Cesarean duration, within 4-6 hours of fetal delivery)
- Uterine Tone Numerical Rating Score, 7 Minutes After Fetal Delivery(7 minutes after fetal delivery, 5 minutes after initiating study drug infusion)
- Uterine Tone Numerical Rating Score, 12 Minutes After Fetal Delivery(12 minutes after fetal delivery, 10 minutes after initiating study drug infusion)
- Percent Change in Mean Arterial Pressure(every 5 minutes for 30 minutes after study drug infusion initiation, compared to baseline)
- Percent Change in Heart Rate From Baseline(every 5 minutes for 30 minutes after study drug infusion initiation, compared to baseline)
- Total Phenylephrine Requirement(Duration of operating room time, up to 240 minutes)
- Pharmacokinetics of Calcium Chloride - Peak Change in Ionized Calcium From 1 Gram of Calcium Chloride(At Tmax (conclusion of the 10-minute intravenous calcium chloride infusion)
- Pharmacodynamic Effect of Calcium Upon Uterine Tone NRS(Within 20 minutes of study drug administration)
研究者
Jessica Ansari, MD, MS
Clinical Assistant Professor
Stanford University