Clinical trial NCT05027048: Calcium Chloride for Prevention of Blood Loss During Intrapartum Cesarean Delivery
Official title: Calcium Chloride for Prevention of Blood Loss From Uterine Atony During Intrapartum Cesarean Delivery (CALBLOC): a Double Blind, Randomized, Placebo Controlled Trial and Nested Population Pharmacokinetic and Pharmacodynamic Analysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Uterine Atony
Uterine Atony With Hemorrhage
Postpartum Hemorrhage
Cesarean Section Complications
Keywords: calcium chloride
uterine atony
postpartum hemorrhage
cesarean delivery
intrapartum cesarean
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Foundation for Anesthesia Education and Research
name: Society for Obstetric Anesthesia and Perinatology
First posted: 2021-08-30
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind, placebo controlled randomized clinical trial with 1:1 allocation
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Quantitative Blood Loss
timeFrame: measurement occurs at conclusion of operating room case
Secondary outcomes:
measure: Number of Participants With Postpartum Hemorrhage
timeFrame: operative course (within 4-6 hours of fetal delivery)
measure: Number of Participants With Second Line Uterotonic Requirement
timeFrame: within 4 hours of delivery
measure: Number of Patients With a Transfusion Requirement
timeFrame: 96 hours of delivery
measure: Change in Hematocrit From Baseline
timeFrame: 1 day
measure: Total Oxytocin Bolus Requirement
timeFrame: Cesarean duration, within 4-6 hours of fetal delivery
measure: Uterine Tone Numerical Rating Score, 7 Minutes After Fetal Delivery
timeFrame: 7 minutes after fetal delivery, 5 minutes after initiating study drug infusion
measure: Uterine Tone Numerical Rating Score, 12 Minutes After Fetal Delivery
timeFrame: 12 minutes after fetal delivery, 10 minutes after initiating study drug infusion
measure: Fluid Requirement
timeFrame: Operating room duration, usually 2 hours
measure: Percent Change in Mean Arterial Pressure
timeFrame: every 5 minutes for 30 minutes after study drug infusion initiation, compared to baseline
measure: Percent Change in Heart Rate From Baseline
timeFrame: every 5 minutes for 30 minutes after study drug infusion initiation, compared to baseline
measure: Total Phenylephrine Requirement
timeFrame: Duration of operating room time, up to 240 minutes
measure: Pharmacokinetics of Calcium Chloride - Baseline Ionized Calcium
timeFrame: In the operating room prior to study drug administration (generally <30 minutes prior to fetal delivery and study drug administration)
measure: Pharmacokinetics of Calcium Chloride - Peak Change in Ionized Calcium From 1 Gram of Calcium Chloride
timeFrame: At Tmax (conclusion of the 10-minute intravenous calcium chloride infusion
measure: Pharmacodynamic Effect of Calcium Upon Uterine Tone NRS
timeFrame: Within 20 minutes of study drug administration
Other outcomes:
measure: Quantitative Blood Loss, Subgroup Quantitative Blood Loss (QBL, mL), Excluding Cases of Documented Non-atonic Bleeding
timeFrame: Calculated at conclusion of operating room case
Locations:
city: Pacifica
country: United States
facility: Jessica Ansari
state: California
Study officials:
affiliation: Stanford University
name: Jessica Ansari, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.