Pharmacokinetic Equivalence of Calcium Gluconate and Calcium Chloride in Parturients

NCT05973747 | Completed Early Phase 1 FDA Drug

• 1 other identifier: 70603
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Postpartum Hemorrhage; Pregnancy Related; Hypocalcemia; Parturition Complication

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (4)

• Serum pH

  Baseline prior to calcium infusion, 6 minutes, 10 minutes, 15 minutes, 30 minutes, 60 minutes after initiation of infusion

• Baseline serum ionized calcium concentration

  Baseline prior to calcium infusion

• Peak change in serum ionized calcium concentration (mmol/L)

  Measured immediately at completion of the 10-minute calcium infusion.

• Time to half of peak change in ionized calcium (minutes)

  10-60 minutes after infusion initiation

Study Arms (2)

Calcium Gluconate

EXPERIMENTAL

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

Calcium Chloride

ACTIVE COMPARATOR

0.5mg calcium chloride, infused intravenously over 10 minute infusion beginning upon umbilical cord clamping

Drug: Calcium chloride

Interventions

Calcium Gluconate DRUG

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 Gluconate

Calcium chloride DRUG

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

Calcium Chloride

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Parturients all biologically female at birth by necessity
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Lucile Packard Children's Hospital

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Postpartum Hemorrhage; Hypocalcemia

Interventions

Calcium Gluconate; Calcium Chloride

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Water-Electrolyte Imbalance

Intervention Hierarchy (Ancestors)

Gluconates; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Calcium Compounds; Inorganic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds

Study Officials

• Jessica Ansari, MD, MS

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor of Anesthesiology

Study Record Dates

• First Submitted: July 13, 2023
• First Posted: August 3, 2023
• Study Start: August 19, 2023
• Primary Completion: December 15, 2023
• Study Completion: December 15, 2023
• Last Updated: April 11, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)