Trial · Interventional

CompletedPhase 1/2Results postedRegistry data

Calcium Chloride for Prevention of Uterine Atony During Cesarean

NCTNCT03867383Other id43076

Open at ClinicalTrials.govAsk about this trial

This trial does not test a peptide that PepBank tracks.

Measures Oxytocin, does not give it. It appears in an outcome measure.

Overview

Status: Completed
Phase: Phase 1/2
Enrollment: 40 participants (actual)
Sponsor: Stanford University · Other
Design: Randomized · Quadruple masking
Countries: 1 country
United States
Start: 15 Mar 2019
Primary completion: 30 Jul 2021
Completion: 15 Aug 2021
First posted: 8 Mar 2019
Last update posted: 28 Apr 2022
Conditions: Uterine Atony · Uterine Atony With Hemorrhage · Cesarean Section Complications

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

2019202020212022

Ph 1/2
Calcium Chloride for Prevention of Uterine Atony During Cesarean
NCT03867383
15 Mar 2019 to 15 Aug 2021

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

Calcium ChlorideDrug
PlaceboDrug

Arms2

Experimental
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.
Placebo comparator
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.

Primary outcomes1

Outcomes the sponsor listed as primary.

Uterine Atony
Time frame · From time of fetal delivery until 4 hours after fetal delivery
Registry description
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

Secondary outcomes(11)

Grading of Uterine Tone
Time frame · A one-time value collected 10 minutes after Cesarean fetal delivery
Registry description
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.
Estimated Blood Loss
Time frame · Immediately upon surgery completion, as patient exits operating theater
Registry description
In milliliters. By blinded obstetrician, taking into account drape, sponge, and suction canister contents
Change in Hematocrit
Time frame · Drawn on postoperative day 1 as standard care
Registry description
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.
Total Crystalloid During Cesarean
Time frame · During entire Cesarean delivery record (generally about 2 hours)
Registry description
Amount of saline administered during cesarean
Maximum Increase in Heart Rate From Baseline (Beats Per Minute)
Time frame · first 45 minutes after study drug completion
Registry description
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
Maximal Decrease in Heartrate From Baseline
Time frame · 45 minutes after study drug infusion is complete
Registry description
Heart rate monitored for 45 minutes after study drug infusion (well past peak)
Maximal Increase in Mean Arterial Blood Pressure From Baseline
Time frame · While in the operating room, generally about 2 hours
Registry description
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.
Maximal Decrease in Mean Arterial Blood Pressure From Baseline
Time frame · While in the operating room, generally about 2 hours
Registry description
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.
Baseline Ionized Calcium Concentration
Time frame · Prior to study drug (up to 5 minutes for blood draw)
Registry description
Ionized calcium levels measured by phlebotomy. Analyzed prior to any study drug administration.
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)
Registry description
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).
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)
Registry description
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

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeCount of participants· From time of fetal delivery until 4 hours after fetal delivery

Uterine Atony

Group	Value (Participants)
Calcium Chloride	4
Placebo	10

Secondary and other outcome results(7)

Secondary outcomeMedian· A one-time value collected 10 minutes after Cesarean fetal delivery

Grading of Uterine Tone

Group	Value (score on a scale)
Calcium Chloride	89
Placebo	80

Secondary outcomeMedian· Immediately upon surgery completion, as patient exits operating theater

Estimated Blood Loss

Group	Value (milliters)
Calcium Chloride	750
Placebo	850

Secondary outcomeMean· Drawn on postoperative day 1 as standard care

Change in Hematocrit

Group	Value (hematocrit (%))	Spread
Calcium Chloride	7.7	4.4
Placebo	6.7	2.6

Secondary outcomeMedian· During entire Cesarean delivery record (generally about 2 hours)

Total Crystalloid During Cesarean

Group	Value (mL)
Calcium Chloride	1200
Placebo	1750

Secondary outcomeMean· first 45 minutes after study drug completion

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

Group	Value (beats per minute)	Spread
Calcium Chloride	15.4	8.8
Placebo	14.2	7.7

Secondary outcomeMean· 45 minutes after study drug infusion is complete

Maximal Decrease in Heartrate From Baseline

Group	Value (beats per minute)	Spread
Calcium Chloride	19.1	13.1
Placebo	16.7	14.4

Secondary outcomeMedian· While in the operating room, generally about 2 hours

Maximal Increase in Mean Arterial Blood Pressure From Baseline

Group	Value (mmHg)
Calcium Chloride	15.4
Placebo	14.2

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Calcium ChlorideNon-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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	0 / 20	0 / 20	6 / 20
PlaceboNon-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. Placebo: 60 milliliters normal saline	0 / 20	0 / 20	6 / 20

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

More studies

1 study on this page

Indexing hint: Randomized controlled trial · 2022

Calcium chloride for the prevention of uterine atony during cesarean delivery: A pilot randomized controlled trial and pharmacokinetic study.

Ansari et al. 2022Journal of clinical anesthesiacited by 11

PMID 35447502DOI 10.1016/j.jclinane.2022.110796PUB-35447502

Full text at the publisher

Publisher page

Eligibility

Who could join, as posted.

Sex: Female
Age: from 18 Years up to 50 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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

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