Clinical trial NCT03867383: Calcium Chloride for Prevention of Uterine Atony During Cesarean
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Uterine Atony
Uterine Atony With Hemorrhage
Cesarean Section Complications
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2019-03-08
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients are randomized via stratified, permuted block randomization to receive a single dose of either calcium chloride 1 gram administered intravenously or placebo at the time of fetal delivery.
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Uterine Atony
timeFrame: From time of fetal delivery until 4 hours after fetal delivery
Secondary outcomes:
measure: Grading of Uterine Tone
timeFrame: A one-time value collected 10 minutes after Cesarean fetal delivery
measure: Estimated Blood Loss
timeFrame: Immediately upon surgery completion, as patient exits operating theater
measure: Change in Hematocrit
timeFrame: Drawn on postoperative day 1 as standard care
measure: Total Crystalloid During Cesarean
timeFrame: During entire Cesarean delivery record (generally about 2 hours)
measure: Maximum Increase in Heart Rate From Baseline (Beats Per Minute)
timeFrame: first 45 minutes after study drug completion
measure: Maximal Decrease in Heartrate From Baseline
timeFrame: 45 minutes after study drug infusion is complete
measure: Maximal Increase in Mean Arterial Blood Pressure From Baseline
timeFrame: While in the operating room, generally about 2 hours
measure: Maximal Decrease in Mean Arterial Blood Pressure From Baseline
timeFrame: While in the operating room, generally about 2 hours
measure: Baseline Ionized Calcium Concentration
timeFrame: Prior to study drug (up to 5 minutes for blood draw)
measure: Clearance of Calcium Chloride
timeFrame: 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)
measure: Volume of Distribution of Calcium Chloride
timeFrame: 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)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Lucile Packard Children's Hospital
state: California
Study officials:
affiliation: Stanford University
name: Brendan Carvalho, MBBCh FRCA
role: STUDY_CHAIR
References:
citation: Ansari JR, Kalariya N, Carvalho B, Flood P, Guo N, Riley E. Calcium chloride for the prevention of uterine atony during cesarean delivery: A pilot randomized controlled trial and pharmacokinetic study. J Clin Anesth. 2022 Sep;80:110796. doi: 10.1016/j.jclinane.2022.110796. Epub 2022 Apr 18.