Administration Of Calcium Gluconate for The Reduction of Blood Loss During Elective Cesarean Delivery

NCT06235749 | Recruiting

• 1 other identifier: RMB-0605-22
• Study Type: interventional
• Target: 1,180
• Locations: 1 country
• Sites: 4

Brief Summary

Postpartum hemorrhage (PPH) is the leading cause of death related to pregnancy. PPH can lead to blood transfusion, disseminated intravascular coagulation (DIC), hysterectomy, or death. The prophylactic administration of uterotonic agents as part of an active management of the third stage of labor has been proven to reduce rates of PPH. However, even with these treatments, PPH rate is still relatively high, and puts women at risk of heavy bleeding and death. Calcium is a key component in the coagulation cascade and known as factor IV. It has a role in platelet activation, and it is an important co-factor for the activation of factors II and There is a concentration-dependent effect of hypocalcemia on in vitro clot strength in patients at risk of bleeding. Calcium gluconate is the calcium salt of gluconic acid, and it has a relatively strong safety profile. Hypocalcemia is a poor prognostic factor in actively bleeding patients. Calcium has a positive inotropic effect both on skeletal muscle and smooth muscle. The inotropic effect doesn't skip the myometrium, and it is well-established that hypocalcemia can impair myometrial contractility. As so, calcium channel blockers are prescribed as a tocolytic drug and calcium gluconate should be considered as adjuvant therapy for treating PPH duo to atony, in case of prolonged tocolytic or magnesium sulfate use prior to delivery. Studies have already shown an association between low ionized calcium levels and the risk for severe bleeding. In a pilot randomized controlled trial of patients with risk factors for uterine atony, calcium was shown to reduce uterine atony compared to placebo. However, current studies have small sample size and are limited to a high-risk population. There are no recommendations in current guidelines for monitoring calcium levels or prescribing calcium as a prophylactic measure for the third stage of labor, despite atony and coagulopathy being significant causes of PPH. HYPOTHESIS: Administration of Calcium Gluconate at the third stage of elective Cesarean delivery will decrease the rates of blood loss during and after the surgery by reducing the rates of uterine atony and development of coagulopathy, thus has the potential of reducing the incidence of PPH and its complications without severe side effects.

Conditions

Elective Cesarean Delivery

Outcome Measures

Primary Outcomes (1)

• Change in mean hemoglobin drop

  Change in mean hemoglobin drop after cesarean delivery at the Calcium gluconate arm, compared to the control arm.

  24 hours after the surgery

Secondary Outcomes (9)

• The rate of women with a decrease of hemoglobin levels of 2 gr/dl or more

  24 hours after the surgery

• additional therapy for the management of PPH

  during hospitalization, an average of 4 days

• Receipt of blood products.

  during hospitalization, an average of 4 days

• treatment with intravenous ferrous (iron).

  during hospitalization, an average of 4 days

• estimated blood loss during the surgery.

  during the surgery

Study Arms (2)

calcium gluconate

EXPERIMENTAL

Administration of Calcium Gluconate 10% IV following umbilical cord clamping.

Drug: Calcium Gluconate 10%

normal saline 0.9%

PLACEBO COMPARATOR

Administration of normal saline 0.9% IV following umbilical cord clamping.

Drug: sodium chloride 0.9%

Interventions

Calcium Gluconate 10% DRUG

Administration of Calcium Gluconate 10% IV following umbilical cord clamping

calcium gluconate

sodium chloride 0.9% DRUG

Administration of sodium chloride 0.9% IV following umbilical cord clamping

normal saline 0.9%

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Elective Cesarean Delivery, at Gestational age of 35 weeks or more.

You may not qualify if:

• Age younger than 18 years old.
• Patients treated with calcium channel blockers.
• Chronic renal failure and hyperphosphatemia.
• Sarcoidosis.
• Hypocalcemia (ionized Ca\<1 mmol/L) or hypercalcemia (ionized Ca\> 1.3 mmol/L) before the surgery.
• Any QT abnormalities as evident by ECG before Calcium Gluconate administrations or any known conduction abnormality.

Sponsors & Collaborators

• Rambam Health Care Campus: lead

Study Sites (4)

Soroka Medical Center

Beersheba, Israel

RECRUITING

Shamir Medical Center

Be’er Ya‘aqov, Israel

RECRUITING

Rambam Medical Center

Haifa, 3525408, Israel

RECRUITING

Edith Wolfson Medical Center

Holon, Israel

RECRUITING

Related Publications (9)

• Deneux-Tharaux C, Bonnet MP, Tort J. [Epidemiology of post-partum haemorrhage]. J Gynecol Obstet Biol Reprod (Paris). 2014 Dec;43(10):936-50. doi: 10.1016/j.jgyn.2014.09.023. Epub 2014 Nov 6. French.

  PMID: 25447386 BACKGROUND

• Palta S, Saroa R, Palta A. Overview of the coagulation system. Indian J Anaesth. 2014 Sep;58(5):515-23. doi: 10.4103/0019-5049.144643.

  PMID: 25535411 BACKGROUND

• Ho KM, Yip CB. Concentration-dependent effect of hypocalcaemia on in vitro clot strength in patients at risk of bleeding: a retrospective cohort study. Transfus Med. 2016 Feb;26(1):57-62. doi: 10.1111/tme.12272. Epub 2016 Jan 5.

  PMID: 26729371 BACKGROUND

• Papandreou L, Chasiotis G, Seferiadis K, Thanasoulias NC, Dousias V, Tsanadis G, Stefos T. Calcium levels during the initiation of labor. Eur J Obstet Gynecol Reprod Biol. 2004 Jul 15;115(1):17-22. doi: 10.1016/j.ejogrb.2003.11.032.

  PMID: 15223159 BACKGROUND

• Korytny A, Klein A, Marcusohn E, Freund Y, Neuberger A, Raz A, Miller A, Epstein D. Hypocalcemia is associated with adverse clinical course in patients with upper gastrointestinal bleeding. Intern Emerg Med. 2021 Oct;16(7):1813-1822. doi: 10.1007/s11739-021-02671-6. Epub 2021 Mar 2.

  PMID: 33651325 BACKGROUND

• Epstein D, Freund Y, Marcusohn E, Diab T, Klein E, Raz A, Neuberger A, Miller A. Association Between Ionized Calcium Level and Neurological Outcome in Endovascularly Treated Patients with Spontaneous Subarachnoid Hemorrhage: A Retrospective Cohort Study. Neurocrit Care. 2021 Dec;35(3):723-737. doi: 10.1007/s12028-021-01214-3. Epub 2021 Apr 7.

  PMID: 33829378 BACKGROUND

• Kawarabayashi T, Kishikawa T, Sugimori H. Effects of external calcium, magnesium, and temperature on spontaneous contractions of pregnant human myometrium. Biol Reprod. 1989 May;40(5):942-8. doi: 10.1095/biolreprod40.5.942.

  PMID: 2765618 BACKGROUND

• Epstein D, Solomon N, Korytny A, Marcusohn E, Freund Y, Avrahami R, Neuberger A, Raz A, Miller A. Association between ionised calcium and severity of postpartum haemorrhage: a retrospective cohort study. Br J Anaesth. 2021 May;126(5):1022-1028. doi: 10.1016/j.bja.2020.11.020. Epub 2020 Dec 17.

  PMID: 33341222 BACKGROUND

• Ansari JR, Kalariya N, Carvalho B, Flood P, Guo N, Riley E. Calcium chloride for the prevention of uterine atony during cesarean delivery: A pilot randomized controlled trial and pharmacokinetic study. J Clin Anesth. 2022 Sep;80:110796. doi: 10.1016/j.jclinane.2022.110796. Epub 2022 Apr 18.

  PMID: 35447502 BACKGROUND

MeSH Terms

Interventions

Sodium Chloride

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Gili Buchnik Fater, MD

CONTACT

+972-54-6738628; gili.buchnik@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2023
• First Posted: February 1, 2024
• Study Start: November 14, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

IL (4)