Clinical trial NCT03064568
Conditions: Myomectomy; Surgical Blood Loss
Keywords: Myomectomy, Misoprostol, Vasopressin, Blood loss
Sponsor: The University of Texas Health Science Center at San Antonio
Start date: 2016-10-14; Completion date: 2024-06-18
Enrollment: 18 participants; Allocation: RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Purpose is to identify if misoprostol in addition to local vasopressin decreases blood loss when compared to vasopressin alone, which is our current practice at this time. The study will be double-blinded with neither the patient nor the researcher knowing whether the placebo or the misoprostol was given. We will monitor patients for decrease in hemoglobin and hematocrit, need for transfusion, and operative time among other measures of perioperative morbidity to see if the addition of misoprostol makes a significant difference. We will also observe patients to see if there are any side effects of misoprostol that make its use undesirable.

Detailed description:
All women with planned myomectomy receive Depo Leupron prior to surgery per standard care and undergo routine pre-operative laboratory testing including hemoglobin and hematocrit. If enrolled in the study, patients will be consented at their pre-op appointment for the study and be asked to complete a visual analog scale to assess pre-operative pain. Patients will be randomized to receive misoprostol 800mcg per rectum or an identical inert tablet(s) per rectum 30 minutes preoperatively. Randomization will be performed by a third party so that neither the surgeon nor patient will know which intervention was performed, and interventions will be placed in sealed, sequentially numbered, opaque envelopes. Researcher team will have all needed data corresponding with randomized code which will be broken at conclusion of study and will be able to match code with patient's initials and medical record number after study completion to analyze data. Myomectomy will then be performed per standard care with the use of local vasopressin to aid in decreasing blood loss per our normal standard of care.

Arms: arm 1: Patients will receive misoprostol 800mcg per rectum 30 minutes preoperatively. arm 2: Patients will receive identical inert tablets per rectum 30 minutes preoperatively.
Interventions: intervention 1: Misoprostol 200Mcg Tab intervention 2: Placebo
Intervention descriptions: intervention 1: 4 tablets will be inserted rectally intervention 2: None

Protocol documents:
Prot_SAP_000.pdf: 
15-554H, Robinson, Form BC, 09-13-21, AMD.docx 
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COVER PAGE  
 
 
 
 
 
Official Study Title: Rectal Misoprostol as a Hemostatic 
Agent During Abdominal Myomectomy 
 
 
NCT number: NCT03064568 
 
 
IRB Approval Date: 09.13.2021 
 
 
Unique Protocol ID: HSC20150554H 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


15-554H, Robinson, Form BC, 09-13-21, AMD.docx 
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Item 1 UTHSCSA 
Tracking Number 
HSC20150554H:  
 
Title: Rectal Misoprostol as a Hemostatic Agent During Abdominal Myomectomy 
 
Item 2 Abstract / Project Summary 
Provide a succinct and accurate description of the proposed 
research. State the purpose/aims. Describe concisely the research 
design and methods for achieving the stated goals. This section 
should be understandable to all members of the IRB, scientific and 
non-scientific.   
DO NOT EXCEED THE SPACE PROVIDED. 
Purpose/Objectives: Determine if rectal misoprostol decreases bleeding during abdominal myomectomy 
 
Research Design/Plan: Enroll women undergoing abdominal myomectomy to either receive preoperative rectal misoprostol or an 
inert tablet and determine if there is a significant difference in blood loss, need for transfusion, decrease in postoperative 
hemoglobin and hematocrit, postoperative pain, and side-effects from medications.   
 
Methods: Prospective double-blinded study completed at a tertiary care center. We plan to enroll 75 participants and monitor pre-
operative, intra-operative, and post-operative variables to determine if there is a significant difference in any of the above 
measures. 
 
Clinical Relevance: To determine if pre-operative rectal misoprostol administration decreases blood loss and need for transfusion 
in women undergoing abdominal myomectomy. 
 
 
 
Item 3 
Background 
 
Describe past experimental 
and/or clinical findings 
leading to the formulation 
of your study.   
For research involving 
unapproved drugs, 
describe animal and 
human studies.   
For research that involves 
approved drugs or devices, 
describe the FDA approved 
uses of this drug/device in 
relation to your protocol. 
Uterine fibroids are very common, affecting up to 70% of Caucasian women and 80% of African-
American women by age 50 in the United States1. When symptomatic, they can cause symptoms 
including abnormal uterine bleeding, pressure-like pain, infertility, and recurrent pregnancy loss, and 
often surgical intervention is indicated2. Many methods have been described for decreasing blood loss 
during myomectomy including intramyometrial vasopressin3, intravenous oxytocin4, tourniquets5, 
intramyomal bupivacaine plus epinephrine6, morcellation7, rectal misoprostol8, and uterine artery 
ligation9. At our institution, the injection of  vasopressin near the myoma is commonly used to 
decrease the amount of bleeding during the procedure3. Recently an article was published by 
Frederick et al that examined the use of misoprostol and perivascular vasopressin versus vasopressin 
alone and found a significant decrease in the amount of bleeding8. Vasopressin in that study was 
administered in a way that is different compared to our usual practice, but the novel concept was the 
addition of preoperative misoprostol. Misoprostol is FDA-approved for prevention of NSAID-induced 
gastric ulcers, but has been used extensively in obstetrics and gynecology to cause cervical ripening, to 
induce or augment uterine contractions, and treatment of postpartum hemorrhage due to atony. It 
has also been reported in other studies to decrease uterine bleeding when administered prior to 
myomectomy10-12. Our objective is to determine if it contributes to decreased blood loss when 
combined with local vasopressin. We have based our sample size calculation on the study done by 
Frederick et al to find a minimum difference of 1.4 with a p-value of 0.58. 
1. 
Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in 
black and white women: ultrasound evidence. Am J Obstet Gynecol. Jan 2003;188(1):100-107. 
2. 
Buttram VC, Reiter RC. Uterine leiomyomata: etiology, symptomatology, and management. Fertil Steril. Oct 
1981;36(4):433-445. 
3. 
Frederick J, Fletcher H, Simeon D, Mullings A, Hardie M. Intramyometrial vasopressin as a haemostatic agent 
during myomectomy. Br J Obstet Gynaecol. May 1994;101(5):435-437. 
4. 
Agostini A, Ronda I, Franchi F, et al. Oxytocin during myomectomy: a randomized study. Eur J Obstet Gynecol 
Reprod Biol. Feb 2005;118(2):235-238. 


15-554H, Robinson, Form BC, 09-13-21, AMD.docx 
 vSept3-2014                                                                                                                                                                                                                                                       3 
5. 
Kathiresan AS, Brookfield KF, Gonzalez-Quintero VH, Verma U. Vasopressin versus a combination of 
vasopressin and tourniquets: a comparison of blood loss in patients undergoing abdominal myomectomies. 
Aust N Z J Obstet Gynaecol. Feb 2011;51(1):79-83. 
6. 
Zullo F, Palomba S, Corea D, et al. Bupivacaine plus epinephrine for laparoscopic myomectomy: a randomized 
placebo-controlled trial. Obstet Gynecol. Aug 2004;104(2):243-249. 
7. 
Chen C. Laparoscopic myomectomy for large myomas. Int Surg. 2006 Sep-Oct 2006;91(5 Suppl):S77-80. 
8. 
Frederick S, Frederick J, Fletcher H, Reid M, Hardie M, Gardner W. A trial comparing the use of rectal 
misoprostol plus perivascular vasopressin with perivascular vasopressin alone to decrease myometrial 
bleeding at the time of abdominal myomectomy. Fertil Steril. Oct 2013;100(4):1044-1049. 
9. 
Sinha R, Sundaram M, Mahajan C, Raje S, Kadam P, Rao G. Laparoscopic myomectomy with uterine artery 
ligation: review article and comparative analysis. J Gynecol Endosc Surg. Jan 2011;2(1):3-10. 
10. 
Celik H, Sapmaz E. Use of a single preoperative dose of misoprostol is efficacious for patients who undergo 
abdominal myomectomy. Fertil Steril. May 2003;79(5):1207-1210. 
11. 
Kongnyuy EJ, Wiysonge CS. Interventions to reduce haemorrhage during myomectomy for fibroids. Cochrane 
Database Syst Rev. 2014;8:CD005355. 
12. 
Ragab A, Khaiary M, Badawy A. The Use of Single Versus Double Dose of Intra-vaginal Prostaglandin E2 "Misoprostol" 
prior to Abdominal Myomectomy: A Randomized Controlled Clinical Trial. J Reprod Infertil. Jul 2014;15(3):152-156. 
Item 4 
Purpose and rationale 
Insert purpose, objectives 
and research 
questions/hypotheses 
here. 
 If you cut and paste from 
another document, make 
sure the excerpted 
material answers the 
question 
Insert purpose: Purpose is to identify if misoprostol in addition to local vasopressin decreases blood 
loss when compared to vasopressin alone, which is our current practice at this time. The study will be 
double-blinded with neither the patient nor the researcher knowing whether the placebo or the 
misoprostol was given. We will monitor patients for decrease in hemoglobin and hematocrit, need for 
transfusion, and operative time among other measures of perioperative morbidity to see if the 
addition of misoprostol makes a significant difference. We will also observe patients to see if there are 
any side effects of misoprostol that make its use undesirable.   
 
 
Item 5 
Study Population(s) Being 
Recruited 
 
In your recruitment plan, how 
many different populations of 
prospective subjects do you plan to 
target? Provide number: 1  
 
 
 
Identify the criteria for inclusion: 
 
 
Identify the criteria for exclusion: 
 
 
 
e.g., a population can be individuals 
with type 2 diabetes controlled with 
diet and/or a population of healthy 
controls.  Or a population can be 
individuals attending an education 
program, etc. 
 
List each different population on a 
separate row and provide a short 
descriptive label:   
(e.g., normal-healthy, diabetics, 
parents, children, etc.) 
 
To add rows use copy & paste 
Normal-healthy adult female  
Female age 20-50 y/o who plan to undergo 
abdominal myomectomy for symptomatic 
myomatous uterus, single attending 
surgeon to perform case to keep other 
factors equivalent. 
Patient with contraindication to misoprostol 
or vasopressin, personal history or cardiac 
or pulmonary disease, history of prior 
myomectomy 
 
 


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Item 6 
Research Plan / Description of the Research Methods a.  Provide a comprehensive narrative describing the research methods.   
Provide the plan for data analysis (include as applicable the sample size calculation). 
 
Step-by-Step Methods: We plan to recruit study participants from women who presented for surgical management of 
myomatous uterus at UTHSCSA MARC clinic and University Downtown REI clinic and who plan to undergo abdominal 
myomectomy. These women all undergo full history and physical exam including transvaginal sono per standard care. All 
women with planned myomectomy receive Depo Leupron prior to surgery per standard care and undergo routine pre-
operative laboratory testing including hemoglobin and hematocrit. If enrolled in the study, patients will be consented at their 
pre-op appointment for the study and be asked to complete a visual analog scale to assess pre-operative pain. Patients will be 
randomized to receive misoprostol 800mcg per rectum or an inert tablet(s) per rectum 30 minutes preoperatively. Since 
initiation of this research study, the shape of misoprostol has changed.  The Investigator and his associates have made multiple 
attempts and have reached out to multiple pharmacies to identify a new vendor for a placebo that has the same color and 
shape as the misoprostol.  Unfortunately, we have been unable to find a placebo that is similar to the drug.  Given this new 
obstacle we pose that a physician or REI fellow will assist as part of this research.  The third-party physician will administer the 
misoprostol/ or placebo rectally as dictated by the protocol.  The PI and all those associated with this research during the 
procedure will turn their backs and not have view of the medication that is administered.  This will maintain blinding. This will 
not pose any additional risks for the patient, and blinding will be maintained. Randomization will be performed by a third party 
(FORU) so that neither the surgeon nor patient will know which intervention was performed, and interventions will be placed 
in sealed, sequentially numbered, opaque envelopes. Researcher team will have all needed data corresponding with 
randomized code which will be broken at conclusion of study and will be able to match code with patient's initials and MRN 
after study completion to analyze data. Myomectomy will then be performed per standard care with the use of local 
vasopressin to aid in decreasing blood loss per our normal standard of care. Length of skin incision, surgical time, enucleation 
time, number of uterine incisions, number of myomas, size of myomas, weight of myomas, estimated blood loss, need for 
transfusion, and complications will be recorded. Estimated blood loss will be calculated by the addition of the blood in the 
aspiration canister combined with the estimated blood on lap sponges. Postoperatively, patients will be monitored 24 hours 
post-op in the hospital for febrile morbidity and need for transfusion; they will also undergo repeat hemoglobin and 
hematocrit measurement 24 hours postoperatively. Patient pain will be assessed with the visual analog scale prior to discharge 
from hospital. All patients will also be asked about any associated side-effects of misoprostol prior to discharge including fever, 
chills, and/or diarrhea.  
 
 
Data Analysis Plan:  Differences in categorical variables will be calculated using the chi-square or Fisher’s exact t-test. 
Continuous variable will be analyzed using independent t-test.  
 
Sample size/power calculation: 
 


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Item 7 Risks Section: 
Complete the following table to describe the risks of all research procedures listed in Step 2, Institutional Form (items 28-34).  Do not list risks of Routine care 
procedures here.  
 ☒ N/A, Risks are described in the informed consent document – do not complete this table. 
Research procedures 
 
example: 
• 
History and physical 
• 
Questionnaire 
• 
Laboratory tests 
 
Add or delete rows as needed 
Risks 
 
List the reasonably expected risks 
under the following categories as appropriate: