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

July 15, 2026 updated by: Rambam Health Care Campus

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

After signing a consent form prior to the surgery (at the pre-operative assessment), At the third stage of labor, women who gave their consent to participate in the study will get either 10 ml of Calcium Gluconate 10% solution (containing 0.94 gr of calcium gluconate) diluted in 100 ml of normal saline IV or 110 ml of normal saline IV.

The solutions will be given in addition to Carbetocin (a long acting oxytocin analogue), in both arms. The invastigators will use calcium gluconate during even-numbered months and normal saline during odd-numbered months, or vice versa, according to randomization that will be known to the primary researcher alone.

A blood sample will be drawn at the beginning of the surgery and sent for blood gas analysis, determining ionized calcium levels and coagulation profile. Women with hypocalcemia or hypercalcemia will be excluded from the trial. Only patients with normal calcium levels between 1.0-1.3 mmol/L will be included in this trial.

An ECG strip will be done prior to the surgery, making sure that the patient doesn't suffer from a QT segment abnormality. All patients will be monitored with a 3 lead- ECG prior, during, and 2 hours following calcium administration. Patients with QT interval abnormalities will be excluded from the trial. After the surgery, a blood sample will be drawn and sent to blood gas analysis (determining ionized calcium levels) and for coagulation profile. A complete blood count will be routinely taken for all women the next day. The hemoglobin level will be compared to the hemoglobin level prior to CD.

Decreased mean hemoglobin drop is the primary outcome. the secondary outcomes are described below.

After the primary analysis we will perform a subgroup analysis, determine whether women with high risk for PPH (such as overdistended uterus, abnormal placentation, myomatous uterus, grand multiparty, coagulation disorder, etc.) may benefit from the intervention more than the general population of all participants.

Study Type

Interventional

Enrollment (Estimated)

1180

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Israel
      • Beersheba, Israel
      • Be’er Ya‘aqov, Israel
        • Recruiting
        • Shamir medical center
        • Contact:
        • Contact:
          • Zohar Goren, MD
      • Haifa, Israel, 3525408
      • Holon, Israel
        • Recruiting
        • Edith Wolfson Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: calcium gluconate
Administration of Calcium Gluconate 10% IV following umbilical cord clamping.
Drug: Calcium Gluconate 10%
Administration of Calcium Gluconate 10% IV following umbilical cord clamping
Placebo Comparator: normal saline 0.9%
Administration of normal saline 0.9% IV following umbilical cord clamping.
Drug: sodium chloride 0.9%
Administration of sodium chloride 0.9% IV following umbilical cord clamping

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in mean hemoglobin drop
Time Frame: 24 hours after the surgery
Change in mean hemoglobin drop after cesarean delivery at the Calcium gluconate arm, compared to the control arm.
24 hours after the surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The rate of women with a decrease of hemoglobin levels of 2 gr/dl or more
Time Frame: 24 hours after the surgery
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
Time Frame: during hospitalization, an average of 4 days
additional therapy for the management of PPH
during hospitalization, an average of 4 days
Receipt of blood products.
Time Frame: during hospitalization, an average of 4 days
Receipt of blood products.
during hospitalization, an average of 4 days
treatment with intravenous ferrous (iron).
Time Frame: 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.
Time Frame: during the surgery
estimated blood loss during the surgery.
during the surgery
Hospitalization length of stay.
Time Frame: an average of 4 days
Hospitalization length of stay.
an average of 4 days
Duration of cesarean delivery
Time Frame: during the surgery
Duration of cesarean delivery
during the surgery
A composite of adverse maternal outcomes
Time Frame: during hospitalization, an average of 4 days
A composite of adverse maternal outcomes including at least one of the following: admission to intensive care unit (NICU), the need for a surgical treatment for uncontrolled PPH, massive blood transfusion (defined as transfusion of ≥10 units red blood cells (RBCs) in 24 hours, disseminated intravascular coagulation (DIC), and death.
during hospitalization, an average of 4 days
Endometritis or antibiotic treatment following CD.
Time Frame: during hospitalization, an average of 4 days
Endometritis or antibiotic treatment following CD.
during hospitalization, an average of 4 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rambam Health Care Campus

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 14, 2023

Primary Completion (Estimated)

May 31, 2028

Study Completion (Estimated)

July 31, 2028

Study Registration Dates

First Submitted

November 20, 2023

First Submitted That Met QC Criteria

January 29, 2024

First Posted (Actual)

February 1, 2024

Study Record Updates

Last Update Posted (Actual)

July 16, 2026

Last Update Submitted That Met QC Criteria

July 15, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RMB-0605-22

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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