Calcium Chloride for Prevention of Uterine Atony During Cesarean

NCT03867383 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 43076
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Uterine Atony; Uterine Atony With Hemorrhage; Cesarean Section Complications

Outcome Measures

Primary Outcomes (1)

• Uterine Atony

  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

  From time of fetal delivery until 4 hours after fetal delivery

Secondary Outcomes (11)

• 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

Study Arms (2)

Calcium Chloride

EXPERIMENTAL

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.

Drug: Calcium Chloride

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Calcium Chloride DRUG

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

Also known as: calcium chloride intravenous, IV calcium

Calcium Chloride

Placebo DRUG

60 milliliters normal saline

Also known as: Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Study being conducted in pregnant women undergoing Cesarean delivery
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Lucile Packard Children's Hospital

Stanford, California, 94305, United States

Location

Related Publications (1)

• 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.

  PMID: 35447502 DERIVED

MeSH Terms

Conditions

Uterine Inertia

Interventions

Calcium Chloride; Calcium; Sodium Chloride

Condition Hierarchy (Ancestors)

Dystocia; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Calcium Compounds; Inorganic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Metals, Alkaline Earth; Elements; Metals; Blood Coagulation Factors; Biological Factors; Sodium Compounds

Limitations and Caveats

This was a pilot study not designed to definitively assess primary and secondary outcomes.

Results Point of Contact

• Title: Dr. Jessica Ansari
• Organization: Stanford University

jansari@stanford.edu

760-845-0328

Study Officials

• Brendan Carvalho, MBBCh FRCA

  Stanford University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: April 20, 2018
• First Posted: March 8, 2019
• Study Start: March 15, 2019
• Primary Completion: July 30, 2021
• Study Completion: August 15, 2021
• Last Updated: April 28, 2022
• Results First Posted: April 28, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)