Calcium Chloride for Prevention of Uterine Atony During Cesarean

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

Sponsors

Lead Sponsor: Stanford University

Source Stanford University
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.

Overall Status Recruiting
Start Date 2019-03-15
Completion Date 2023-03-30
Primary Completion Date 2021-04-30
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Uterine atony From time of fetal delivery until 4 hours after fetal delivery
Secondary Outcome
Measure Time Frame
Pharmacokinetics of calcium chloride in pregnant women minutes after drug delivery (0-90)
Grading of uterine tone A one-time value collected 10 minutes after Cesarean fetal delivery
Quantitative blood loss Immediately upon surgery completion, as patient exits operating theater
Average heart rate (beats per minute) 15 minutes after study drug infusion is complete
Average blood pressure (millimeters mercury) 15 minutes after study drug infusion is complete
Cumulative Phenylephrine dose (micrograms per kilogram) During entire Cesarean delivery record (generally about 2 hours)
Side effect: pain at IV site During or in the 30 minutes after study drug infusion
Side effect: arrhythmia including tachycardia or bradycardia During or in the 30 minutes after study drug infusion
Change in hematocrit Drawn on postoperative day 1 as standard care
Enrollment 40
Condition
Intervention

Intervention Type: Drug

Intervention Name: Calcium Chloride

Description: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline

Arm Group Label: Calcium Chloride

Intervention Type: Drug

Intervention Name: Placebo

Description: 60 milliliters normal saline

Arm Group Label: Placebo

Other Name: Saline

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

Gender:

Female

Gender Based:

Yes

Gender Description:

Study being conducted in pregnant women undergoing Cesarean delivery

Minimum Age:

18 Years

Maximum Age:

50 Years

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Brendan Carvalho, MBBCh FRCA Study Chair Stanford University
Overall Contact

Last Name: Jessica R Ansari, MD

Phone: 760-845-0328

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: Lucile Packard Children's Hospital Brendan Carvalho, MBBCh, FRCA 650-861-8607 [email protected]
Location Countries

United States

Verification Date

2020-10-01

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Stanford University

Investigator Full Name: Brendan Carvalho

Investigator Title: Professor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Calcium Chloride

Type: Experimental

Description: 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.

Label: Placebo

Type: Placebo Comparator

Description: 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.

Patient Data Undecided
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

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

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description: 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.

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