Carbetocin with calcium chloride to improve uterine contraction after elective cesarean

Effect of Co-administration of Carbetocin and Calcium Chloride on Uterine Tone in Patients Undergoing Elective Cesarean Delivery: a Double-blind Randomized Control Trial

This trial will test whether giving carbetocin together with calcium chloride helps the uterus stay contracted and reduces bleeding during scheduled cesarean deliveries at term.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years to 45 Years
• Sex: Female
• Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital (other)
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT07187544 on ClinicalTrials.gov

What this trial studies

In a double-blind, randomized trial at a single center, people having an elective cesarean at or beyond 37 weeks under neuraxial anesthesia are randomized to receive carbetocin with either calcium chloride or placebo. The interventions are given around the time of uterotonic administration and clinicians measure uterine tone and blood loss during and after the operation. Patients with known high-risk factors for uterine atony or certain medical contraindications (for example recent digoxin use or significant kidney disease) are excluded. The aim is to determine whether adding calcium to a longer-acting uterotonic (carbetocin) reduces postpartum hemorrhage or the need for additional uterotonic interventions.

Who should consider this trial

Good fit: Ideal candidates are pregnant people scheduled for an elective cesarean at ≥37 weeks who will receive neuraxial anesthesia and do not have major risk factors for uterine atony or contraindications like recent digoxin use or significant kidney disease.

Not a fit: Patients with high-risk conditions for atony (for example placenta previa/accreta, grand multiparity, multiple gestation, macrosomia, prior severe PPH), those on contraindicated medications, or with advanced kidney disease are unlikely to be eligible or to benefit from the intervention tested here.

Why it matters

Potential benefit: If successful, this approach could reduce blood loss and lower the need for extra medications or surgical interventions after cesarean delivery.

How similar studies have performed: Prior randomized work combining calcium with oxytocin showed no overall reduction in blood loss though a subgroup signal suggested benefit in atony, and combining calcium specifically with carbetocin is relatively novel in settings where carbetocin is not routinely available.

Eligibility criteria

Inclusion Criteria:

1. Scheduled CD for patients ≥ 37 weeks excluding high risk factors for uterine atony
2. Neuraxial anesthesia as the primary anesthetic where intrathecal medications are the primary anesthetic

Exclusion Criteria:

1. Risk factors for uterine atony including:

   1. Overdistended uterus due to fetal macrosomia reported on prenatal ultrasound \>90th centile or \> 4000 gm, multiple gestation, grand multiparity (≥5 births at ≥ 20 weeks gestation), polyhydramnios
   2. History of uterine atony/PPH (documented with blood loss \> 2000 ml, blood transfusion, use of surgical methods such as Bakri balloon, B-Lynch sutures, uterine artery ligation or embolization)
   3. Obesity with body mass index (BMI) \> 40 kg/m2
   4. Placenta previa and/or placenta accreta
2. Digoxin therapy within 14 days (hypercalcemia can exacerbate digoxin toxicity)
3. Patients needing intraoperative IV ceftriaxone or tetracycline.
4. Kidney disease including Stage 3 chronic kidney disease, serum creatinine above 120 mmol/L or GFR \<60 ml/min (to prevent hypercalcemia due to reduced creatinine clearance in those with impaired kidney function as calcium is renally excreted)
5. Calcium channel blockade within 24 hours (opposing effect)
6. Known history of cardiac disease including arrhythmias, ischemia, and congenital heart disease (to avoid attributing cardiac symptoms to study drugs)
7. Preexisting hypertension, preeclampsia or persistent elevated blood pressure above 160/100 mmHg requiring treatment
8. Emergency cesarean deliveries or women in labor
9. Planned general anesthetic for patients where neuraxial is contraindicated.

Where this trial is running

Toronto, Ontario

• Mount Sinai Hospital — Toronto, Ontario, Canada (RECRUITING)

Study contacts

• Principal investigator: Mrinalini Balki, MD — MOUNT SINAI HOSPITAL
• Study coordinator: Mrinalini Balki, MD

Conditions: Postpartum Hemorrhage, calcium, carbetocin, cesarean