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NCT Number: NCT03867383

Calcium Chloride for Prevention of Uterine Atony During Cesarean

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.

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Key information

Conditions

Uterine Atony Cesarean Section Complications Dystocia Female Urogenital Diseases and Pregnancy Complications Obstetric Labor Complications Pregnancy Complications Urogenital Diseases Uterine Atony With Hemorrhage Uterine Inertia

Age range

18 year–50 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Lucile Packard Children's Hospital

Stanford, California, 94305, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Calcium chloride

Drug

All included in intervention description.

1 gram of calcium chloride in total 60 milliliters normal saline

Other names: calcium chloride intravenous, IV calcium

Placebo

Drug

60 milliliters normal saline

Other names: Saline

Primary outcomes

  1. Uterine Atony

    Time frame: 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:

    • Administration of > 1 bolus of oxytocin
    • Increase in the oxytocin infusion rate above the standard 7.5units/hour
    • Administration of a second line uterotonic including methylergonovine, carboprost, or misoprostol
    • Mechanical surgical interventions for uterine atony including placement of an intrauterine balloon, B-lynch sutures, or O'Leary sutures
    • Requirement for embolization of the uterine arteries by interventional radiology
    • Estimated blood loss> 1000 milliliters
    • Transfusion of blood products during or within 4 hours of Cesarean

Secondary outcomes

  1. Grading of Uterine Tone

    Time frame: A one-time value collected 10 minutes after Cesarean fetal delivery

    Subjective assessment of uterine tone by the obstetrician, from 0-100%.

    Obstetricians were blinded to study assignment arm, and were instructed that 0% indicates a completely atonic (un-contracted) uterus, and 100% indicates a perfectly, firmly contracted uterus. They were asked to provide this score by palpating the fundus (top) of the uterus as soon as the study drug infusion was complete.

  2. Estimated Blood Loss

    Time frame: Immediately upon surgery completion, as patient exits operating theater

    In milliliters. By blinded obstetrician, taking into account drape, sponge, and suction canister contents

  3. Change in Hematocrit

    Time frame: Drawn on postoperative day 1 as standard care

    Changes from preoperative to standard postoperative day 1 hematocrit in patients. The hematocrit represents the percentage by volume of red blood cells in a blood sample and decreases after losing blood. The change in hematocrit was calculated by subtracting the number obtained the morning after surgery from the number obtained prior to surgery.

  4. Total Crystalloid During Cesarean

    Time frame: During entire Cesarean delivery record (generally about 2 hours)

    Amount of saline administered during cesarean

  5. Maximum Increase in Heart Rate From Baseline (Beats Per Minute)

    Time frame: first 45 minutes after study drug completion

    Heart rate is recorded every minute throughout delivery. Heart rate values over the first 45 minutes after study drug completion will be compared to baseline calcium chloride to placebo group

  6. Maximal Decrease in Heartrate From Baseline

    Time frame: 45 minutes after study drug infusion is complete

    Heart rate monitored for 45 minutes after study drug infusion (well past peak)

  7. Maximal Increase in Mean Arterial Blood Pressure From Baseline

    Time frame: While in the operating room, generally about 2 hours

    Baseline mean arterial pressure was established upon entry into the operating room after at least 3 minutes had passed since positioning onto the operating room bed and prior to commencement of the cesarean delivery or to block placement. Mean arterial blood pressure was recorded every 5 minutes from this baseline timepoint until completion of the cesarean. Maximal increase was calculated as the difference between the baseline and the highest recorded mean arterial blood pressure.

  8. Maximal Decrease in Mean Arterial Blood Pressure From Baseline

    Time frame: While in the operating room, generally about 2 hours

    Baseline mean arterial pressure was established upon entry into the operating room after at least 3 minutes had passed since positioning onto the operating room bed and prior to commencement of the cesarean delivery or to block placement. Mean arterial blood pressure was recorded every 5 minutes from this baseline timepoint until completion of the cesarean. Maximal decrease was calculated as the difference between the baseline and the lowest recorded mean arterial blood pressure.

  9. Baseline Ionized Calcium Concentration

    Time frame: Prior to study drug (up to 5 minutes for blood draw)

    Ionized calcium levels measured by phlebotomy. Analyzed prior to any study drug administration.

  10. Clearance of Calcium Chloride

    Time frame: 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)

    Pharmacokinetic parameters were analyzed based upon ionized calcium concentrations over time. Blood calcium concentration was measured at the following time points: baseline (pre-drug delivery), 0-20 minutes after drug administration, and 20-90 minutes after delivery. The reported values for concentration over time were obtained using NONMEM (Non Linear Mixed Effects Modeling).

  11. Volume of Distribution of Calcium Chloride

    Time frame: 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)

    Pharmacokinetic parameters were analyzed based upon ionized calcium concentrations over time. Blood calcium concentration was measured at the following time points: baseline (pre-drug delivery), 0-20 minutes after drug administration, and 20-90 minutes after delivery. The resulting values for concentration over time were evaluated with NONMEM

Sponsors and collaborators

Lead sponsor

Stanford University

Other

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2021
Study completion
2021
First posted
Mar 8, 2019
Registry last updated
Apr 28, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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