Effect of Oral Calcium Carbonate on Uterine Contractility and Labor Outcomes: A Randomized Controlled Trial
Phase: PHASE2
Conditions: Uterine Contraction, Labor Complication, Labor Active Dilated Cm, Labor Dystocia, Labor Duration, Labor, Labor Delivery
Sponsor: Arrowhead Regional Medical Center

 
 
Title: 
Effect of Oral Calcium Carbonate on Uterine Contractility 
and Labor Outcomes: A Randomized Controlled Trial 
Short Title 
RCT: Oral Calcium Supplementation in Labor 
 
 
NCT Number: 
pending 
Protocol Date: 
4-26-24 
 
 
Principal Investigators 
 
Tina Bui, DO  
Michelle Nelson, RN  
Preeanka Mazumder, MD  
Kristina Roloff, DO, MPH, MFM 
Guillermo J Valenzuela, MD, MFM, MBA 
 
Arrowhead Regional Medical Center 
Department of Women’s Health 
400 N. Pepper Avenue, Colton CA 92373 
Work: (909) 580-6825/ (909) 580-3470 
 
email: Valenzuelag@armc.sbcounty.gov 
 
 
 
 
 
 
 

II: Introduction/Literature review:  
 
In the United States, cesarean delivery rates affect one in three women, with labor 
dystocia frequently cited as a leading cause.1 Labor dystocia can arise from various 
factors such as fetal size, positioning, pelvic structure, contractions, or maternal 
conditions.1 Clinically we can only correct the amount of uterine activity by oxytocin 
administration ± amniotomy. The inability to decrease the cesarean section rate has 
prompted exploration for additional strategies. 
 
One proposed method to improve uterine activity that has sparked interest in numerous 
social group forums is oral calcium carbonate supplementation, yet it remains largely 
unstudied in a clinical setting. Both calcium and carbonate components are recognized 
for enhancing myometrial contractility.2 Physiologically, calcium plays a vital role in 
regulating uterine contractility throughout pregnancy.2 Oxytocin triggers the release of 
calcium ions from intracellular stores via L-type Calcium channels within myometrial 
cells, inducing action potentials and thereby uterine contractility.3 During labor, there's 
an upsurge in calcium channel expression, facilitating uterine contractility.3 Additionally, 
serum calcium levels have been correlated with uterine contractility, as patients with 
higher calcium levels are more likely to deliver vaginally compared to those undergoing 
cesarean delivery.2 4-6 
 
Given its potential to enhance uterine contractility and potentially reduce the need for 
surgical intervention, we aim to investigate the effects of calcium carbonate on uterine 
contractility. We hypothesized that giving calcium carbonate intrapartum can improve 
uterine contractility and decrease the number of cesarean deliveries.  
 
III: Objectives:  research question, purpose of the study, hypothesis 
• Research questions:  
o Does calcium carbonate supplementation intrapartum improve uterine 
contractility, assessed by measuring Montevideo units, contraction 
frequency, and peak contraction strength.  
• Purpose of the Study: The purpose of the study is to investigate whether calcium 
carbonate supplementation during labor can improve uterine contractility and 
decrease labor dystocia. By conducting this trial, the aim is to provide evidence-
based guidance to healthcare providers regarding the potential use of calcium 
carbonate as a preventive measure for labor dystocia.  
• Hypothesis: We hypothesized that pregnant women, those who receive calcium 
carbonate supplementation will have improve uterine contractility and a shorter 
labor course. 
• Alternative Hypothesis: Calcium supplementation will have no effect on 
contractility  
 
IV: Study type: Randomized control trial    
 
V: Methods:  
• Location: Labor and Delivery at Arrowhead Regional Medical Center  

• Start: Plan to start at the receipt of IRB approval. We anticipate the duration of 
the study to be about 2 years.   
• Type of research: other 
• Inclusion:  
§ Patients undergoing induction of labor with an intrauterine pressure 
catheter already in place at the discretion of the OB provider  
§ Maternal age: >18 years of age 
§ Gestational age > 37 weeks 0 day  
§ Cephalic presentation  
§ Able to understand/read English and/or Spanish 
• Exclusion: 
§ Maternal age < 18 years of age  
§ Incarcerated patients  
§ Active labor  
§ Active illicit substance use  
§ Multiple fetal gestations 
§ Bleeding concerning for hemorrhage/placental abruption/placenta 
previa, or other contraindications to vaginal delivery 
§ Aneuploidy or fetal structural anomaly  
§ Prior cesarean deliveries  
§ Known maternal arrhythmias, hyperparathyroidism, heart failure, 
kidney failure, liver failure, and history of kidney stones  
§ Medications that affect uterine contractility like Magnesium, 
Terbutaline, Cytotec (need to be 4 hours after administration to 
enroll) 
 
• Subject recruitment: All women with a term pregnancy, admitted for induction of 
labor will be asked to participate if age >18 years of age and English/Spanish 
speaking. We will plan to recruit when a patient is at least 4 cm and greater with 
an IUPC already in place. Using a baseline Montevideo unit of 200, if we were to 
aim for a 20% difference with a power of 80%, a sample size of 80 would be the 
minimum goal to enroll. Therefore, our goal is to enroll at least 40 patients into 
each group.  
 
• Consent: 
o The informed consent process will be conducted by trained research staff 
and will include all aspects of the study and a full disclosure of the risks, 
benefits, procedures, and alternatives.  The study consent and HIPAA 
authorization will be signed after all questions have been discussed and 
answered.  Collection of baseline information, including such items as 
contact information, BP measurements, demographic and pregnancy 
history information, concomitant medications, and lifestyle information will 
follow the informed consent process.  
o All data will be kept confidential to comply with HIPAA regulations. No 
patient identifiers will be included in the data sets. All data will be kept in a 
password protected folder within the ARMC network and will only be made 

available to study investigators. The database will be controlled, and 
password-protected. 
o All data and records will be kept confidential in accordance with 
Institutional policies and HIPAA. There will be extremely limited access to 
subject information. All data will be anonymized before publication. Patient 
Data Sets will include identifiers that are strictly limited to medical record 
number, ethnicity, age and sex, along with associated clinical data. Patient 
Data Sets will be imported into password protected Excel files located in 
an encrypted folder accessible only to the investigators involved in the 
study, IRB, and IT on the ARMC server. All published poster 
presentations, abstracts and papers will be de-identified, with a medical 
record numbers and any other identifying material removed. Patient’s age, 
parity, sex and race will be used in publication for educational purposes. 
 
VI: Study Design and analysis:  
● All patients admitted for term induction of labor will be asked to participate if they 
meet the inclusion criteria as described above. Once consented, the participants 
will be randomly allocated into two groups: control versus intervention group. 
Randomization will be done as block randomization based on maternal BMI at 
time of admission, all odd patients will be enrolled into the control group and all 
even study numbers will be in the intervention group.  
-Control group: no medication  
-Intervention group: Calcium carbonate 500 mg 4 tablets PO x1 
-Calcium carbonate (TUMS) is an over-the-counter antacid medication 
and common side effects include changes in bowel habits like constipation 
or diarrhea, bloating, gas, and abdominal discomfort. Rare side effects 
include allergic reactions and hypercalcemia if taken in large amounts. 
The daily recommended max dose is 8000mg, we will be giving a max of 
2000 mg.7 
● The primary outcome will determine the effect of calcium carbonate on uterine 
contraction strength, assessed by comparing Montevideo units (MVU), frequency 
of contractions, and peak of the contractions 30 minutes before medication 
administration and at 30 minutes interval for a total of 2 hours afterward. To 
ensure accuracy in MVU measurement, all patients should already have an 
intrauterine pressure catheter (IUPC) in place at the discretion of the OB provider 
before they are enrolled. Secondary outcomes include duration of first and 
second stage of labor, mode of delivery, neonatal outcomes (NICU admission, 
low APGAR scores), and maternal outcomes (PPH). 
● Other maternal information such as height, weight, BMI, age, parity, race, 
gestational age, cervical dilation/effacement/station at the time of medication 
administration and after administration, time to delivery, oxytocin use, epidural 
use, Apgars, perineal laceration, QBL, birthweight, mode of delivery, delivery 
complications will be obtained to compare among the two groups to make sure 
there are no confounding factors. Since Pitocin dose is a confounding variable 
after receiving the medication, patients must be off Pitocin during study period.   

• The data collected will be divided into 2 groups: control versus intervention 
group. Statistical analysis included descriptive statistics to summarize maternal 
characteristics and clinical outcomes. Normality testing was performed, and 
appropriate comparative statistical tests were selected, including two-way 
Student’s t-tests, Tukey’s tests, or post hoc Student–Newman–Keuls tests as 
appropriate. A p-value of less than 0.05 was considered statistically significant. 
Univariate and multivariate linear regression analyses were conducted to identify 
associations between maternal, fetal, and labor-related variables and study 
outcomes. 
• Uni- and multivariate analysis with linear regression modeling will be used to 
identify significant associations between maternal, fetal, or labor characteristics.  
 
VII: Risks and Benefits: 
• The risks to the study participants are not greater than minimal as the study does 
not change the patient’s plan of care. Calcium carbonate has been shown to be 
safe in pregnancy and should not harm the fetus or the participant. We are using 
less than the maximum recommended dose in pregnancy. The patient's data will 
be stored on a password protected document to decrease the risk of breach of 
confidentiality.  
• These patients are already admitted for induction of labor and have accepted 
those risks, benefits, and alternatives. There are risks with induction of labor, that 
the patient will experience regardless of participation in this study. These risks 
include discomfort, fetal distress, NICU admission, cesarean section, 
hemorrhage, infection, failed or prolonged induction, and maternal mental 
exhaustion. 
• Otherwise, this study has no other intervention that could cause harm.   
• Risks from breaches in confidentiality are limited as described above.  
 
VIII: Funding source: Department of Obstetrics and Gynecology 
 
IX: References:  
 
1. Safe prevention of the primary cesarean delivery. Obstetric Care Consensus No. 
1. American College of Obstetricians and Gynecologists. Obstet Gynecol. Mar 
2014;123;693–711. 
2. Raees, Sabahat et al. “Calcium Carbonate as a Potential Intervention to Prevent 
Labor Dystocia: Narrative Review of the Literature.” Journal of patient-centered 
research and reviews vol. 10,3 128-135. 18 Jul. 2023, doi:10.17294/2330-
0698.2010 
3. Wray S, Jones K, Kupittayanant S, Li Y, Matthew A, Monir-Bishty E, Noble K, 
Pierce SJ, Quenby S, Shmygol AV. Calcium signaling and uterine contractility. J 
Soc Gynecol Investig. 2003 Jul;10(5):252-64. doi: 10.1016/s1071-
5576(03)00089-3.  
4. Aninora, Novia & Seridji, Joserizal & Agus, Meilinda. (2018). Correlation of 
Calcium Levels With The Strength of Uterus Contraction on The Active Phase of 
First Stage Labor. Journal of Midwifery. 3. 76. 10.25077/jom.3.2.76-83.2018. 

5. Pehlivanoğlu, Bilge et al. “A close look at the contraction and relaxation of 
the myometrium; the role of calcium.” Journal of the Turkish German 
Gynecological Association vol. 14,4 230-4. 1 Dec. 2013, 
doi:10.5152/jtgga.2013.67763 
6. 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.  
7. Epocrates. 2024. Drug information: Calcium carbonate. In Epocrates medical 
references.  
8. 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. 
PMID: 37917943. 
 
 

Arrowhead Regional Medical Center 
Informed Consent Form for Participation in a Research Project 
 
Study Title: Randomized Controlled Trial Comparing the Efficacy of Calcium Carbonate for 
Preventing Labor Dystocia 
Principal Investigator: Guillermo Valenzuela 
 
Introduction:  
You are being asked to join a research study.  You are being asked to take part in this study 
because you are being induced with a singleton pregnancy. You do not have to participate in this 
research study.  The main purpose of research is to create new knowledge for the benefit of 
future patients and society in general.  Research studies may or may not benefit the people who 
participate.   
 
Research is voluntary, and you may change your mind at any time. There is no penalty if you 
decide not to participate, or if you start the study and decide to stop early.  Either way, you can 
still get medical care and services at Arrowhead Regional Medical Center. 
 
This consent form explains what you have to do if you are in the study.  It also describes the 
possible risks and benefits.   Please read the form carefully and ask as many questions as you 
need to, before deciding about this research. You can ask questions now or anytime during the 
study.  The researchers will tell you if they receive any new information that might cause you to 
change your mind about participating.   
 
Purpose:  
You are invited to be part of a research study about the effects of calcium on uterine contractions  
 
The purpose of the study is to  assess the effectiveness of calcium carbonate in influencing 
uterine contractility. You are invited to be in this study because you are in labor with a singleton 
pregnancy and we will see how long it takes for you to deliver. 
 
The persons responsible for the research project are Tina Bui, RJ Stowe, Kayla Witcik, Michelle 
Nelson, Kristy Roloff, Guillermo Valenzuela. Your doctor is interested in your health as well as 
conducting this research project. If you feel that your doctor can not represent your best interest, 
you can ask for another doctor to take care of you.  
 
Description of your Involvement:  
If you are eligible and decide to participate in this study, your participation will last 
approximately up until delivery. Your participation will involve taking a medication during in 
labor that may or may not improve your contractions and help one delivery vaginally. The study 
will conclude at the point of delivery. We do not anticipate that these medications will add any 
further discomfort to your labor.  Furthermore, the management of your labor will not change 
based on these medications.  We/I would also record your demographics, medical history 
including pregnancy history, physical exam, vital signs, height and weight for the purpose of this 
study. Your name and identity will be protected.  
 

Risks and Discomforts of Participation: 
There may be some risk or discomfort from your participation in this research. This study 
minimal risk. There are not anticipated health risks for you or your fetus from your participation 
in this research.  Participating in this study will involve the following risks: There are mild 
medication side effects in some people which include constipation and bloating. There may be 
some discomfort while undergoing an induction of labor but is no different than the normal 
course of an induction. The patient's data will be stored on a password protected document to 
decrease the risk of breach of confidentiality.  
 
All records and research materials that identify you will be held confidential. Any published 
document resulting from this study will not disclose your identity without your permission. 
Information identifying you will only be available to the study personnel. All data will be kept in 
a password protected folder within the ARMC network and will only be made available to study 
investigators. The database will be controlled, and password protected. Your rights regarding 
permission to use your health information are described on the attached “Authorization for Use 
of Protected Health Information” form. 
 
There may be other risks of the study that are not yet known. 
Benefits:  
You may or may not directly benefit from this study. Although you may not directly benefit from being in 
this study, others may benefit because of what we learn about the effects of calcium carbonate on labor. 
 
Subject Rights: 
You do not give up any legal rights to privacy, confidentiality, or safety by participating in this study. 
Participating in this study is completely voluntary. Not participating in the study will not be held against 
you and will not affect your access to care or treatment unrelated to this research. Even if you decide to 
participate now, you may change your mind and stop at any time without affecting your medical care. 
Your study doctor or primary care doctor can discuss alternatives with you which may include, not taking 
any additional medications. If you decide to withdraw before this study is completed, your data will not 
be used. You will be given a copy of the California Experimental Subject’s Bill of Rights and a copy of 
this Informed Consent to keep. 
 
Potential Costs: 
You and/or your health insurance must pay for those services, supplies, procedures, and care required for 
routine medical care.  You will be responsible for any co-payments and/or deductibles as required by your 
insurance.  If you participate in this study, there may be additional costs to you, such as travel for study 
visits. 
 
Potential Compensation: 
For your participation in this research project, you will not benefit from this study.  You will not be paid. 
You will not receive any results of the measurements either. The only people who will receive the results 
are the investigators doing the study, and they will not release the results to you or your other physician. 
Any new information developed during the course of this research that may relate to your willingness to 
be a participant will be given to you. If there is good information that comes from the study, we may 
decide to share the information with other physicians through publication of the data. No patient will be 

reported individually, but composite of all patients will be used. In this manner, there is no manner that 
you are identified. 
 
Injured during Study: 
If you feel you have been injured by taking part in this study, consult with a physician or call 911 if the 
situation is a medical emergency.  No funds have been set aside nor any plans made to compensate you 
for time lost for work, disability, pain or other discomforts resulting from your participation in this 
research. 
 
Storage and Future Use of Data: 
Your privacy will be protected and your research records will be confidential. Your data/specimens (will 
be de-identified and used for research. All data sets will be stored in a password protected folder within 
the ARMC network and will only be made available to study investigators. The database is monitored, 
and password protected. The data sets will be kept confidential and available until the study is published 
and then data will be erased.  It is possible that other people may need to see the information you give us 
as part of the study, such as organizations responsible for making sure the research is done safely and 
properly like the Arrowhead Regional Medical Center, government offices or the study sponsor, full 
sponsor name(s), if any. 
 
Contact Information for the Study Team: 
If you have questions about this research, including questions about scheduling or your compensation for 
participating, you may contact Guillermo Valenzuela. 
 
Contact Information for Questions about Your Rights as a Research Participant: 
If you have questions about your rights as a research participant, or wish to obtain information, ask 
questions or discuss any concerns about this study with someone other than the researcher(s), the IRB 
Coordinator is an impartial third party who is not associated with the research. You may address 
complaints or questions about this protocol to this person, who may be contacted at (909) 580-6336. 
 
 
 

 
Participant’s Statement of Consent: 
• 
I have read the contents of the consent form and have listened to the verbal explanation given by 
the investigator. 
• 
My questions concerning this study have been answered to my satisfaction.   
• 
Signing this consent document does not waive my rights nor does it release the investigators, 
institution or sponsors from their responsibilities. 
• 
I hereby give voluntary consent to participate in this study. 
I understand I will be given a copy of this consent form after signing it.  
 
_________________________________________________ 
Printed Name of Participant 
 
______________________________________  
___________ 
Signature of Participant 
 
 
 
Date 
 
Subject is unable to consent/sign because ___________________________________________. 
 
_________________________________________________ 
Printed Name of Legally Authorized Representative  
 
____________________________________________  
 
_____ 
Signature of Legally Authorized Representative  
 
Date 
 
 
Investigator’s Statement 
I have discussed the research project with the participant; have explained all of the information contained 
in the Informed Consent to the participant including any adverse reactions; the participant was 
encouraged to ask questions; and that all questions were answered. 
 
_________________________________________________ 
Printed Name of Investigator 
 
______________________________________  
___________ 
Signature of Investigator 
 
 
 
Date