Pharmacokinetic Equivalence of Calcium Gluconate and Calcium Chloride in Parturients

Pregnancy Related Clinical Trial

Official title:

Pharmacokinetic Equivalence of Calcium Gluconate and Calcium Chloride in Parturients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05973747
• Other study ID #: 70603
• Status: Completed
• Phase: Early Phase 1
• Start date: August 19, 2023
• Est. completion date: December 15, 2023

Study information

• Verified date: April 2024
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: December 15, 2023
• Est. primary completion date: December 15, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemorrhage
• Hypocalcemia
• Postpartum Hemorrhage
• Pregnancy Related

Intervention

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.
• Calcium chloride
0.5 grams of calcium chloride, infused intravenously over 10 minutes upon umbilical cord clamping

Locations

Country	Name	City	State
United States	Lucile Packard Children's Hospital	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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.
Secondary	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