Calcium Chloride in the Prevention of Uterine Atony During Cesarean in Women at Increased Risk of Hemorrhage: a Pilot Randomized Controlled Trial and Pharmacokinetic Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Uterine Atony
研究概览
简要总结
In this pilot study, investigators will administer calcium chloride or placebo to pregnant women undergoing Cesarean delivery who have been identified as high risk for hemorrhage due to poor uterine muscle contraction, or atony. They will assess whether a single dose of calcium given immediately after the delivery of the fetus decreases the incidence of uterine atony and bleeding for the mother. The pharmacokinetics of calcium chloride in pregnant women will also be established. Data from this pilot study of 40 patients will be used to determine sample size and appropriateness of a larger randomized clinical trial.
详细描述
Poor contraction of the uterus, also known as uterine atony, is the leading cause of severe blood loss during Cesarean section, both in the US and worldwide. Exogenous calcium has been shown to increase uterine muscle contraction in in vitro and in animal studies. Calcium is also an essential factor in normal blood clotting. Anesthesiologists commonly administer intravenous calcium chloride during Cesarean as well as other types of surgery, but formal randomized studies to determine efficacy in improving uterine tone have not been performed.
In this pilot, randomized controlled study, the anesthesiologist will administer a one-time dose of intravenous calcium chloride 1gram versus placebo at the time of fetal delivery to women identified as having high risk of hemorrhage during Cesarean delivery. Primary outcome assessed will be a composite measure of uterine atony. Data from the pilot study will be used to perform power and sample size calculations for a larger study. Secondary outcomes assessed will include total blood loss, subjective assessment of uterine tone by the blinded obstetrician performing surgery, safety, side effects, and pharmacokinetic profile of calcium chloride in pregnant women.
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
Randomization has been performed and study ID designation to drug or placebo arm allocated to opaque envelopes prior to subject enrollment. An anesthesiologist not involved in clinical care of the patient or data entry or analysis opens the envelope at the time of subject enrollment and prepares the study drug versus placebo in a 60mL syringe, labeled only with subject ID#. Drug and placebo appear identical as clear solutions and are administered by the same protocol.
The key designating whether each study ID patient received calcium or placebo has been uploaded to the redCAP data entry database and cannot be retrieved without entering a passcode.
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Pregnant female subjects at Lucile Packard Children's hospital / Stanford hospital undergoing Cesarean will be screened for inclusion in the study based upon presence of at least 2 risk factors for uterine atony/ postpartum hemorrhage. The risk factors include the following:
- •intrapartum Cesarean delivery
- •failed operative vaginal delivery with forceps or vacuum
- •magnesium infusion
- •chorioamnionitis
- •multiple gestation
- •polyhydramnios
- •preterm delivery <37 weeks
- •prior history of postpartum hemorrhage
- •labor induction or augmentation with oxytocin
- •advanced maternal age
- •obesity with body mass index >40
排除标准
- •a degree of case urgency to which taking time to consent for the study could compromise patient care, determined by anesthesiologist or obstetrician
- •patient age <18 years or >50 years
- •renal dysfunction with serum Creatinine > 1.0
- •abnormal cardiac function or history of arrhythmia
- •patient taking digoxin
- •patient currently taking a calcium channel blocker for a cardiovascular indication
研究组 & 干预措施
Calcium Chloride
Non-participating anesthesiologist prepares the drug solution, which is 1 gram of calcium chloride diluted into a total volume of 60 milliliters normal saline, labeled only with the study ID number. The solution is administered intravenously utilizing an Alaris syringe pump and microbore tubing, with infusion starting immediately at the time of fetal delivery at a rate of 360 milliliters per hour (for a calcium infusion rate of 100 milligrams /minute until the full 1 gram dose is administered).
This is a one-time administration. Patients continue to receive all standard care during the Cesarean including 1 unit oxytocin bolus at the time of fetal delivery + continuous oxytocin infusion at 7.5 units per hour per our institution's protocol.
干预措施: Calcium Chloride (Drug)
Placebo
Non-participating anesthesiologist prepares the placebo solution, which is 60 milliliters normal saline, labeled only with the study ID number. The solution is administered intravenously utilizing an Alaris syringe pump and microbore tubing, with infusion starting immediately at the time of fetal delivery at a rate of 360 milliliters per hour.
This is a one-time administration. Patients continue to receive all standard care during the Cesarean including 1 unit oxytocin bolus at the time of fetal delivery + continuous oxytocin infusion at 7.5 units per hour per our institution's protocol.
干预措施: Placebo (Drug)
结局指标
主要结局
Uterine Atony
时间窗: From time of fetal delivery until 4 hours after fetal delivery
The primary outcome of interest is the presence of clinical uterine atony, as defined the by any of the following: 1. Administration of \> 1 bolus of oxytocin 2. Increase in the oxytocin infusion rate above the standard 7.5units/hour 3. Administration of a second line uterotonic including methylergonovine, carboprost, or misoprostol 4. Mechanical surgical interventions for uterine atony including placement of an intrauterine balloon, B-lynch sutures, or O'Leary sutures 5. Requirement for embolization of the uterine arteries by interventional radiology 6. Estimated blood loss\> 1000 milliliters 7. Transfusion of blood products during or within 4 hours of Cesarean
次要结局
- Grading of Uterine Tone(A one-time value collected 10 minutes after Cesarean fetal delivery)
- Estimated Blood Loss(Immediately upon surgery completion, as patient exits operating theater)
- Change in Hematocrit(Drawn on postoperative day 1 as standard care)
- Total Crystalloid During Cesarean(During entire Cesarean delivery record (generally about 2 hours))
- Maximum Increase in Heart Rate From Baseline (Beats Per Minute)(first 45 minutes after study drug completion)
- Maximal Decrease in Heartrate From Baseline(45 minutes after study drug infusion is complete)
- Maximal Increase in Mean Arterial Blood Pressure From Baseline(While in the operating room, generally about 2 hours)
- Maximal Decrease in Mean Arterial Blood Pressure From Baseline(While in the operating room, generally about 2 hours)
- Volume of Distribution of Calcium Chloride(Samples drawn at baseline, at random time points after study drug administration while in the operating room, and upon arrival to the recovery room (up to 90 minutes))
- Baseline Ionized Calcium Concentration(Prior to study drug (up to 5 minutes for blood draw))
- Clearance of Calcium Chloride(Samples drawn at baseline, at random time points after study drug administration while in the operating room, and upon arrival to the recovery room (up to 90 minutes))
研究者
Brendan Carvalho
Professor
Stanford University