Elective Cesarean DeliveryNCT06235749
Administration Of Calcium Gluconate for The Reduction of Blood Loss During Elective Cesarean Delivery
A study testing Calcium Gluconate 10% and sodium chloride 0.9% in people with Elective Cesarean Delivery, run by Rambam Health Care Campus at 4 sites in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Elective Cesarean Delivery
- What is being tested?
- Calcium Gluconate 10% and sodium chloride 0.9%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,180 participants
- Where
- 4 sitesIsrael
- Study dates
- 14 Nov 2023to 31 Jul 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Elective Cesarean Delivery, at Gestational age of 35 weeks or more.
Who cannot join
- 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.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Israel4 sites, 4 recruiting
- Recruiting
Shamir Medical Center
Be’er Ya‘aqov
Lee Segev, MD, +972-89779016, Gabbaylee@gmail.com
Zohar Goren, MD
- Recruiting
Soroka Medical Center
Beersheba
Yair Binyamin, MD, +972-8-6400262, yairben1@gmail.com
Offer Erez, MD, offererez@gmail.com
- Recruiting
Rambam Medical Center
Haifa, 3525408
Gili Buchnik Fater, MD, +972-54-6738628, gili.buchnik@gmail.com
Roee Iluz, MD, r_iluz@rambam.health.gov.il
- Recruiting
Edith Wolfson Medical Center
Holon
Liat Mor, MD, +972-35028525, liatmor1@gmail.com
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Elective Cesarean Delivery
- Being tested
- Calcium Gluconate 10%, sodium chloride 0.9%
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Calcium Gluconate 10%Drug
Administration of Calcium Gluconate 10% IV following umbilical cord clamping
sodium chloride 0.9%Drug
Administration of sodium chloride 0.9% IV following umbilical cord clamping
| Study group | Role | What they receive |
|---|---|---|
| calcium gluconate | Experimental | Administration of Calcium Gluconate 10% IV following umbilical cord clamping. Receives: Drug: Calcium Gluconate 10% |
| normal saline 0.9% | Placebo comparator | Administration of normal saline 0.9% IV following umbilical cord clamping. Receives: Drug: sodium chloride 0.9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mean hemoglobin drop
Change in mean hemoglobin drop after cesarean delivery at the Calcium gluconate arm, compared to the control arm.
Measured: 24 hours after the surgery
Secondary outcomes (9)
The rate of women with a decrease of hemoglobin levels of 2 gr/dl or more
The rate of women with a decrease of hemoglobin levels of 2 gr/dl or more.
Measured: 24 hours after the surgery
additional therapy for the management of PPH
additional therapy for the management of PPH
Measured: during hospitalization, an average of 4 days
Receipt of blood products.
Receipt of blood products.
Measured: during hospitalization, an average of 4 days
treatment with intravenous ferrous (iron).
treatment with intravenous ferrous (iron).
Measured: during hospitalization, an average of 4 days
estimated blood loss during the surgery.
estimated blood loss during the surgery.
Measured: during the surgery
Hospitalization length of stay.
Hospitalization length of stay.
Measured: an average of 4 days
Duration of cesarean delivery
Duration of cesarean delivery
Measured: during the surgery
A composite of adverse maternal outcomes
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.
Measured: during hospitalization, an average of 4 days
Endometritis or antibiotic treatment following CD.
Endometritis or antibiotic treatment following CD.
Measured: during hospitalization, an average of 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2024
- Study start14 Nov 2023
- Primary completion31 May 2028 (estimated)
- Study completion31 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Elective Cesarean DeliveryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 1,180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rambam Health Care Campus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06235749
- Sponsor's protocol ID
- RMB-0605-22
- Status last verified
- Jul 2026
- First submitted
- 20 Nov 2023
- Last updated
- 16 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25447386Palta 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.
PubMed 25535411Ho 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.
PubMed 26729371Papandreou 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.
PubMed 15223159Korytny 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.
PubMed 33651325Epstein 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.
PubMed 33829378Kawarabayashi 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.
PubMed 2765618Epstein 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.
PubMed 33341222Ansari 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.
PubMed 35447502