Pharmacokinetic Equivalence of Calcium Gluconate and Calcium Chloride in Parturients

Calcium is a life saving medicine in the care of parturients. It has many important uses including treatment of hypocalcemia, treatment of magnesium toxicity, prevention of hypocalcemia during blood transfusion (of citrate containing blood products), treatment of hyperkalemia, and others. Recent clinical trials also suggest that calcium given after cord clamping may decrease blood loss in patients undergoing cesarean delivery. 2 FDA approved forms of calcium can be given intravenously: calcium chloride and calcium gluconate. Over the last decade there have been times with drug shortages of either calcium chloride or calcium gluconate. So there have been and likely will continue to be times when one formulation or the other may not be adequately available. Despite the importance of calcium and the frequency in which it is used in parturients, there are no published studies in parturients to determine dose equivalence between calcium gluconate and calcium chloride. In this study the investigators will determine the population pharmacokinetics of calcium gluconate and calcium chloride in parturients and calculate the dose equivalent ratio the two drugs. This will help clinicians select appropriate doses of calcium and provide resilience to the drug supply chain in our era of frequent drug shortages.

Study Overview

• Status: Completed
• Conditions: Pregnancy Related; Hypocalcemia; Postpartum Hemorrhage; Parturition Complication
• Intervention / Treatment: Drug: Calcium chloride; Drug: Calcium Gluconate

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Lucile Packard Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Pregnant female subjects delivering at the study institution via scheduled cesarean delivery at term (>=37 weeks gestation)

Exclusion Criteria:

1. severe range blood pressure (BP >160/>110) within the 48 hours prior to delivery
2. patient age <18 years or >45 years
3. renal dysfunction with serum Cr > 1.0 mg/dL
4. known history of congenital or acquired cardiac disease or history of arrhythmia
5. patient taking digoxin
6. patient currently taking a calcium channel blocker
7. Weight <55kg or >100kg, or
8. receiving magnesium infusion within 24 hours prior to or during cesarean delivery
9. administration of intraoperative doses of calcium by the anesthesiology team for clinical indications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Calcium Chloride; 0.5mg calcium chloride, infused intravenously over 10 minute infusion beginning upon umbilical cord clamping	Drug: Calcium chloride; 0.5 grams of calcium chloride, infused intravenously over 10 minutes upon umbilical cord clamping
Experimental: Calcium Gluconate; Infused intravenously over 10 minutes upon umbilical cord clamping. First 10 assigned patients received 2 grams per protocol. Subsequent 13 patients received 1.5 grams, dose recalibrated per protocol.	Drug: Calcium Gluconate; Infused intravenously over 10 minutes upon umbilical cord clamping. First 10 assigned patients received 2 grams per protocol. Subsequent 13 patients received 1.5 grams, dose recalibrated per protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bioequivalent ratio of calcium gluconate (g) to calcium chloride (g)	Calculated via NONMEM	Using data gathered from serial lab draws at 5 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes after initiation of infusion
Clearance from first to second compartment (L/min)	Determined using population pharmacokinetic analysis in NONMEM	Using data gathered from serial lab draws at 5 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes after initiation of infusion
Volume of distribution of first compartment of pharmacokinetic model (L)	Determined using population pharmacokinetic analysis in NONMEM	Using data gathered from serial lab draws at 5 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes after initiation of infusion
Clearance from second compartment (L/min)	Determined using population pharmacokinetic analysis in NONMEM	Using data gathered from serial lab draws at 5 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes after initiation of infusion
Volume of distribution of second compartment of pharmacokinetic model (L)	Determined using population pharmacokinetic analysis in NONMEM	Using data gathered from serial lab draws at 5 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes after initiation of infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum pH	Serum pH will be measured in each participant from a maximum of 6 venous blood draws of 0.5mL (1/10th of a teaspoon). These blood draws will be the same blood draws used to measure serum ionized calcium concentration, no additional blood draws will be necessary. These draws will occur at the following target times: prior to calcium administration, at 6 minutes, 10 minutes, 15 minutes, minutes, minutes after beginning calcium administration. The serum pH levels will be immediately analyzed using an Abbott iStat machine.	Baseline prior to calcium infusion, 6 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes after initiation of infusion
Baseline serum ionized calcium concentration	Ionized calcium will be measured in each participant prior to administration of the 10-minute calcium infusion. The ionized blood calcium levels will be immediately analyzed using an Abbott iStat machine.	Baseline prior to calcium infusion
Peak change in serum ionized calcium concentration (mmol/L)	Measured via venous blood draw and an Abbott iStat CG8+ cartridge	Measured immediately at completion of the 10-minute calcium infusion.
Time to half of peak change in ionized calcium (minutes)	A two-compartment model does not lend itself to a meaningful half-life approximation. However, the time to serum values measuring 1/2 of the peak change in ionized calcium can be calculated from the pharmacokinetic model	10-60 minutes after infusion initiation

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Jessica Ansari, MD, MS, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2023
• Primary Completion (Actual): December 15, 2023
• Study Completion (Actual): December 15, 2023

Study Registration Dates

• First Submitted: July 13, 2023
• First Submitted That Met QC Criteria: July 25, 2023
• First Posted (Actual): August 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Calcium Metabolism Disorders; Water-Electrolyte Imbalance; Uterine Hemorrhage; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hemorrhage; Postpartum Hemorrhage; Hypocalcemia; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium; Calcium, Dietary
• Other Study ID Numbers: 70603

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes