Calcium Chloride for Prevention of Blood Loss During Intrapartum Cesarean Delivery

NCT05027048 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: 62206MRTG-02-15-2022-AnsariYIG-2020
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity and mortality worldwide. Up to 80% of PPH is caused by uterine atony, the failure of the uterine smooth muscle to contract and compress the uterine vasculature after delivery. Laboratory and epidemiological studies show that low extracellular and serum calcium levels, respectively, decrease uterine contractility. A pilot study performed by the investigators supports the hypothesis that intravenous calcium chloride is well tolerated and may have utility in preventing uterine atony. The proposed research will establish the relationship between uterine tone and calcium through a clinical trial with an incorporated pharmacokinetic and pharmacodynamic (PK/PD) study. In a randomized, placebo-controlled, double-blind trial, investigators will establish the effect of 1 gram of intravenous calcium chloride upon quantitative blood loss and uterine tone during cesarean delivery in parturients with high risk of uterine atony. Investigators will concurrently collect serial venous blood samples to measure calcium for PK/PD modeling in this pregnant study cohort. High-quality clinical research and development of novel therapeutics to manage uterine atony are critical to reduce the high maternal morbidity and mortality from PPH.

Conditions

Uterine Atony; Uterine Atony With Hemorrhage; Postpartum Hemorrhage; Cesarean Section Complications

Keywords

calcium chloride; uterine atony; postpartum hemorrhage; cesarean delivery; intrapartum cesarean

Outcome Measures

Primary Outcomes (1)

• Quantitative Blood Loss

  Standardized volumetric and gravimetric assessment of blood loss during cesarean. Note: will analyze all participants, but planned subgroup analysis will also occur excluding patients with non-atonic reasons for blood loss including hysterotomy extension, placental abruption, cervical or vaginal laceration, etc

  measurement occurs at conclusion of operating room case

Secondary Outcomes (14)

• Number of Participants With Postpartum Hemorrhage

  operative course (within 4-6 hours of fetal delivery)

• Number of Participants With Second Line Uterotonic Requirement

  within 4 hours of delivery

• Number of Patients With a Transfusion Requirement

  96 hours of delivery

• Change in Hematocrit From Baseline

  1 day

• Total Oxytocin Bolus Requirement

  Cesarean duration, within 4-6 hours of fetal delivery

Other Outcomes (1)

• Quantitative Blood Loss, Subgroup Quantitative Blood Loss (QBL, mL), Excluding Cases of Documented Non-atonic Bleeding

  Calculated at conclusion of operating room case

Study Arms (2)

Calcium chloride

EXPERIMENTAL

1 gram of calcium chloride in total volume 60mL with sterile saline, delivered over 10 minute controlled infusion at a constant rate (360mL/hour) beginning 2 minutes after fetal delivery and 1 minute after delayed cord clamp. This intervention occurs IN ADDITION TO standard care with oxytocin 2 unit bolus and infusion at 7.5 units per hour which begins immediately after fetal delivery.

Drug: Calcium chloride

Saline placebo

PLACEBO COMPARATOR

60mL sterile saline, delivered over 10 minute controlled infusion at a constant rate (360mL/hour) beginning 2 minutes after fetal delivery and 1 minute after delayed cord clamp. This intervention occurs IN ADDITION TO standard care with oxytocin 2 unit bolus and infusion at 7.5 units per hour which begins immediately after fetal delivery.

Drug: Saline placebo

Interventions

Calcium chloride DRUG

See arm description above

Calcium chloride

Saline placebo DRUG

see arm description above

Saline placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patient had a trial of labor for vaginal delivery prior to cesarean
• Patient received an oxytocin infusion for labor augmentation or induction prior to cesarean

You may not qualify if:

• renal dysfunction with serum Cr \>1.0 mg/dL
• known underlying cardiac condition
• treatment with digoxin within the last 2 weeks for a maternal or fetal indication
• treatment with a calcium channel blocker medication within 24 hours
• hypertension necessitating intravenous antihypertensive medication within 24 hours
• emergent case in which study participation could in any way impede patient care by the judgement of the obstetrician, anesthesiologist, or bedside nurse

Sponsors & Collaborators

• Stanford University: lead
• Foundation for Anesthesia Education and Research: collaborator
• Society for Obstetric Anesthesia and Perinatology: collaborator

Study Sites (1)

Jessica Ansari

Pacifica, California, 94044, United States

Location

Related Publications (2)

• Cole NM, Abushoshah I, Fields KG, Carusi DA, Robinson JN, Bateman BT, Farber MK. The interrater reliability and agreement of a 0 to 10 uterine tone score in cesarean delivery. Am J Obstet Gynecol MFM. 2021 May;3(3):100342. doi: 10.1016/j.ajogmf.2021.100342. Epub 2021 Feb 27.

  PMID: 33652161 BACKGROUND

• Ansari JR, Yarmosh A, Michel G, Lyell D, Hedlin H, Cornfield DN, Carvalho B, Bateman BT. Intravenous Calcium to Decrease Blood Loss During Intrapartum Cesarean Delivery: A Randomized Controlled Trial. Obstet Gynecol. 2024 Jan 1;143(1):104-112. doi: 10.1097/AOG.0000000000005441. Epub 2023 Nov 3.

  PMID: 37917943 RESULT

MeSH Terms

Conditions

Uterine Inertia; Postpartum Hemorrhage

Interventions

Calcium Chloride

Condition Hierarchy (Ancestors)

Dystocia; 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

Intervention Hierarchy (Ancestors)

Calcium Compounds; Inorganic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds

Results Point of Contact

• Title: Dr. Jessica Ansari
• Organization: Stanford

jansari@stanford.edu

650-723-5349

Study Officials

• Jessica Ansari, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The patient, obstetrician, anesthesiologist, and clinical research staff will be blinded to the intervention. Drugs will be labeled only as "study drug"
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Model Details: Double blind, placebo controlled randomized clinical trial with 1:1 allocation

Study Record Dates

• First Submitted: August 18, 2021
• First Posted: August 30, 2021
• Study Start: April 4, 2022
• Primary Completion: March 29, 2023
• Study Completion: April 3, 2023
• Last Updated: June 11, 2024
• Results First Posted: June 11, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)