Trial Outcomes & Findings for Calcium Chloride for Prevention of Uterine Atony During Cesarean (NCT NCT03867383)

NCT ID: NCT03867383

Last Updated: 2022-04-28

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 40 participants
• Primary outcome timeframe: From time of fetal delivery until 4 hours after fetal delivery
• Results posted on: 2022-04-28

Participant Flow

Participant milestones

Measure	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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	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. Placebo: 60 milliliters normal saline
Overall Study STARTED	20	20
Overall Study COMPLETED	20	20
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Calcium Chloride for Prevention of Uterine Atony During Cesarean

Baseline characteristics by cohort

Measure	Calcium Chloride n=20 Participants 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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	Placebo n=20 Participants 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. Placebo: 60 milliliters normal saline	Total n=40 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Asian	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Black	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Hispanic/Latina	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · White	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Mixed	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Other/Decline to disclose	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	20 participants n=7 Participants	40 participants n=5 Participants
Gestational age	38.4 weeks of gestation n=5 Participants	39.0 weeks of gestation n=7 Participants	38.6 weeks of gestation n=5 Participants

PRIMARY outcome

Timeframe: 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:

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

Outcome measures

Measure	Calcium Chloride n=20 Participants 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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	Placebo n=20 Participants 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. Placebo: 60 milliliters normal saline
Uterine Atony	4 Participants	10 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Calcium Chloride n=20 Participants 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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	Placebo n=20 Participants 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. Placebo: 60 milliliters normal saline
Grading of Uterine Tone	89 score on a scale Interval 80.0 to 90.0	80 score on a scale Interval 75.0 to 89.0

SECONDARY outcome

Timeframe: Immediately upon surgery completion, as patient exits operating theater

Population: Quantitative blood loss was not able to be performed, so estimated blood loss was used for all participants

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

Outcome measures

Measure	Calcium Chloride n=20 Participants 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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	Placebo n=20 Participants 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. Placebo: 60 milliliters normal saline
Estimated Blood Loss	750 milliters Interval 600.0 to 800.0	850 milliters Interval 650.0 to 1000.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Calcium Chloride n=20 Participants 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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	Placebo n=20 Participants 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. Placebo: 60 milliliters normal saline
Change in Hematocrit	7.7 hematocrit (%) Standard Deviation 4.4	6.7 hematocrit (%) Standard Deviation 2.6

SECONDARY outcome

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

Amount of saline administered during cesarean

Outcome measures

Measure	Calcium Chloride n=20 Participants 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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	Placebo n=20 Participants 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. Placebo: 60 milliliters normal saline
Total Crystalloid During Cesarean	1200 mL Interval 1000.0 to 2000.0	1750 mL Interval 1500.0 to 2000.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Calcium Chloride n=20 Participants 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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	Placebo n=20 Participants 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. Placebo: 60 milliliters normal saline
Maximum Increase in Heart Rate From Baseline (Beats Per Minute)	15.4 beats per minute Standard Deviation 8.8	14.2 beats per minute Standard Deviation 7.7

SECONDARY outcome

Timeframe: 45 minutes after study drug infusion is complete

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

Outcome measures

Measure	Calcium Chloride n=20 Participants 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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	Placebo n=20 Participants 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. Placebo: 60 milliliters normal saline
Maximal Decrease in Heartrate From Baseline	19.1 beats per minute Standard Deviation 13.1	16.7 beats per minute Standard Deviation 14.4

SECONDARY outcome

Timeframe: While in the operating room, generally about 2 hours

Population: All participants

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.

Outcome measures

Measure	Calcium Chloride n=20 Participants 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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	Placebo n=20 Participants 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. Placebo: 60 milliliters normal saline
Maximal Increase in Mean Arterial Blood Pressure From Baseline	15.4 mmHg Interval 11.0 to 19.8	14.2 mmHg Interval 10.3 to 17.8

SECONDARY outcome

Timeframe: While in the operating room, generally about 2 hours

Population: All participants

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.

Outcome measures

Measure	Calcium Chloride n=20 Participants 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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	Placebo n=20 Participants 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. Placebo: 60 milliliters normal saline
Maximal Decrease in Mean Arterial Blood Pressure From Baseline	33.8 mmHg Interval 25.2 to 40.9	32.0 mmHg Interval 21.1 to 43.7

SECONDARY outcome

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

Population: Because this outcome was assessed at baseline prior to study drug administration, participants in the active and placebo groups who consented to phlebotomy were combined for this analysis.

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

Outcome measures

Measure	Calcium Chloride n=24 Participants 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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	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. Placebo: 60 milliliters normal saline
Baseline Ionized Calcium Concentration	1.18 millimol per liter Interval 1.16 to 1.19	—

SECONDARY outcome

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)

Population: Patients who received calcium chloride and consented to blood sampling for PK analysis. Patients who received placebo were not included since they did not receive calcium chloride and had no data collected for the outcome.

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).

Outcome measures

Measure	Calcium Chloride n=13 Participants 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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	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. Placebo: 60 milliliters normal saline
Clearance of Calcium Chloride	0.93 L/min Interval 0.63 to 1.52	—

SECONDARY outcome

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)

Population: Patients who received calcium chloride and consented to blood sampling for PK analysis. Patients who received placebo were not included since they did not receive calcium chloride and had no data collected for the outcome.

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

Outcome measures

Measure	Calcium Chloride n=13 Participants 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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	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. Placebo: 60 milliliters normal saline
Volume of Distribution of Calcium Chloride	76 Liters Interval 49.0 to 91.0	—

Adverse Events

Calcium Chloride

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Calcium Chloride n=20 participants at risk 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. Calcium Chloride: All included in intervention description. 1 gram of calcium chloride in total 60 milliliters normal saline	Placebo n=20 participants at risk 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. Placebo: 60 milliliters normal saline
Product Issues IV line discomfort	5.0% 1/20 • Number of events 1 • Any event within the 5 days of delivery	0.00% 0/20 • Any event within the 5 days of delivery
Gastrointestinal disorders Nausea or vomiting	20.0% 4/20 • Number of events 4 • Any event within the 5 days of delivery	10.0% 2/20 • Number of events 2 • Any event within the 5 days of delivery
Cardiac disorders Hypertension	0.00% 0/20 • Any event within the 5 days of delivery	10.0% 2/20 • Number of events 2 • Any event within the 5 days of delivery
Cardiac disorders Arrhythmia	10.0% 2/20 • Number of events 2 • Any event within the 5 days of delivery	15.0% 3/20 • Number of events 3 • Any event within the 5 days of delivery

Additional Information

Dr. Jessica Ansari

Stanford University

Phone: 760-845-0328

Email: jansari@stanford.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place