Myoma;UterusPhase 4NCT04482959
Intraoperative Carbetocin to Decrease Blood Loss During Hysteroscopic Myomectomy
A Phase 4 study testing Carbetocin and Sodium chloride 0.9% in people with Myoma;Uterus, run by Mansoura University Hospital at 1 site in Egypt.
Trial summary
Submucous myomas represent one of the main indications of operative hysteroscopy. Since 1976 when Neuwirth and Amin reported the first five cases of excision of submucous myomas , several techniques have been developed in order to render hysteroscopic myomectomy a safe and effective procedure . Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Myoma;Uterus
- What is being tested?
- Carbetocin 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
- 40 participants
- Where
- 1 siteEgypt
- Study dates
- 15 Jul 2020to 1 Feb 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Symptomatic women aged 18-45 years diagnosed by transvaginal sonography (TVS) to have single type 0 or I submucous uterine myomas according to FIGO classification system with a largest diameter ≤ 4 cm and myometrial free margin of at least 10 mm.
Who cannot join
- • Age < 18 or > 45 years.
- Uterine septum or structural uterine abnormality (including multiple uterine fibroids and/or multiple submucous myomas)
- Present or history of cervical or uterine malignancies.
- Active pelvic infection.
- Chronic medical diseases (cardiopulmonary, thromboembolic, hepatic, or renal diseases).
- Bleeding disorders.
Show all 9Show fewer
- Patients receiving anticoagulant therapy.
- Patients receiving gonadotropin-releasing hormone (GnRH) analogues.
- History of adverse reaction contraindications for Carbetocin.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Intraoperative Carbetocin to Decrease Blood Loss During Hysteroscopic Myomectomy: a Randomized Controlled Trial
Submucous myomas represent one of the main indications of operative hysteroscopy. Since 1976 when Neuwirth and Amin reported the first five cases of excision of submucous myomas , several techniques have been developed in order to render hysteroscopic myomectomy a safe and effective procedure .
Hysteroscopic myomectomy is currently considered the "gold standard" minimally invasive approach for the treatment of symptomatic submucous myomas . Patients undergoing hysteroscopic myomectomy are liable to significant blood loss, and hemodynamic and hematological disturbances. Excessive bleeding during hysteroscopic myomectomy remains a major challenge for the endoscopic gynecological surgeons. Many interventions were introduced to reduce the risk of bleeding during myomectomy. These include the use of utero-tonics such as oxytocin, or the use of anti-fibrinolytics such as tranexamic acid . The potential advantage of oxytocin infusion during hysteroscopic myomectomy is that it can maintains uterine contractility throughout the procedure, and thus, reduce blood loss .
Carbetocin (1-deamino-1-monocarba-(0-2-methyltyrosine)-oxytocin) is a long-acting synthetic agonist analogue of the human oxytocin. When injected to a woman, it induces uterine contractions . Although many interventions have been described to reduce the intraoperative blood loss during hysteroscopic myomectomy, there is a need for a well-designed randomized controlled trials to identify the most efficient interventions, with reasonable safety profiles, to help the perform a safe and curative surgery.
Read the detailed description
All patients will have preoperative evaluation by gynecologists and anesthetists, with history taking and pelvic examination. A TVS scan will be done to determine the number, size and location of the myomas, and evaluate the myometrial free margin (the minimum thickness between the outer edge of the myoma and inner edge of the uterine serosa), which was found to be ideally ≥ 10 mm (11). Prior office diagnostic hysteroscopy will be performed for evaluation of the number, location and grade of the submucous myomas, and assessment of the endocervical canal and uterine cavity and the position of the tubal ostia in order to aid orientation. Preoperative full blood count, serum creatinine, fasting blood glucose, liver enzymes, coagulation profile ( INR), and viral markers will be done for all the patients. Monopolar resectoscopic myomectomies will be scheduled in the proliferative phase of menstrual cycle by a single experienced operator.
After induction of general anesthesia, immediately before the operation, participants will receive either 1 ml of carbetocin (100 mcg/ml) IV over 1 minute (study group) or 1 ml of sodium chloride 0.9% IV over 1 minute (control group). The procedure will be done using the available standard setup and the distending solution used will be 1.5% glycine. A drape with a fluid-collection pouch (Lingeman 3 in 1 Procedure Drape, Lingeman Medical Products, Inc., Indianapolis, IN) placed beneath the woman's buttocks will be used to collect outflow fluid escaping between the cervix and sheath to prevent spillage of irrigating fluid onto the floor. Fluid inflow and outflow will be monitored every 3-5 minutes. The outflow fluid will be measured to the nearest milliliter. The inflow and outflow volumes of the distension solution will be carefully monitored continuously during the procedure by nurses not involved in the study under the current monitoring protocol at the operating theater. The procedure would be terminated if the fluid imbalance reached 1 L.
After completing the procedure, the surgeon completed a record sheet for rating of bleeding amount and the quality of operative view. Postoperative full blood count will be done for all patients 24 hours after the procedures. Preoperative and postoperative hemoglobin and hematocrit, the need for blood transfusion, the duration of operation, any operative complications and medication adverse effects will be recorded.
- Conditions
- Myoma;Uterus
- Being tested
- Carbetocin, Sodium chloride 0.9%
- Medical subject headings
- Myofibroma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarbetocinDrug
(1-deamino-1-monocarba-(0-2-methyltyrosine)-oxytocin) is a long-acting synthetic agonist analogue of the human oxytocin
Sodium chloride 0.9%Drug
Physiological solution will be used as placebo
| Study group | Role | What they receive |
|---|---|---|
| Carbetocin group | Experimental | This group will contain 20 patients having single type 0 or I submucous uterine myomas according to International Federation of Gynecology and Obstetrics classification system with a largest diameter ≤ 4 cm and myometrial free margin of at least 10 mm.After induction of general anesthesia, immediately before the operation, participants will receive either 1 ml of carbetocin (100 mcg/ml) IV over 1 minute. Receives: Drug: Carbetocin |
| • Control group | Placebo comparator | This group will contain 20 patients having single type 0 or I submucous uterine myomas according to International Federation of Gynecology and Obstetrics classification system with a largest diameter ≤ 4 cm and myometrial free margin of at least 10 mm.After induction of general anesthesia, immediately before the operation, participants will receive either 1 ml of sodium chloride 0.9% IV over 1 minute. Receives: Drug: Sodium chloride 0.9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
intraoperative bleeding amount
Minimal Bleeding is insufficient to interfere with the operation or with the clarity of vision Moderate Bleeding that obscure the visual field and resolves only with continuous and constant irrigation of the distention media Excessive Bleeding that necessitate intervention other than continuous and constant irrigation of the distention media (e.g. controlled only by increasing the pressure to tamponade the bleeding from myoma bed)
Measured: Time Frame: Start with the first resectoscope myoma cut till withdrawal of hysteroscope through the cervix at the end of the procedure
• Change in haemoglobin and hematocrit
- Change in haemoglobin and hematocrit as surrogate measures of haemostatic effect
Measured: Haemoglobin and hematocrit values 24 hours before myomectomy and 24 hour after myomectomy
Secondary outcomes (3)
• Operative time
It evaluate the complication that could affect the technique
Measured: Start with insertion of hysteroscope through the cervix ends with withdrawal of hysteroscopy through the cervix at the end of the procedure
• Fluid deficit
Calculation the fluid deficit between in flow volume and outflow volume.
Measured: start with insertion of hysteroscope through the cervix ends with withdrawal of hysteroscopy through the cervix at the end pf the procedure
• The quality of operative view
Poor When it is not possible to visualize the entire uterine cavity and the cornual areas nor adequate visualization of the myoma during more than half of the procedure despite continuous and constant irrigation of the distention media Fair When it is not possible to visualize the entire uterine cavity and the cornual areas nor adequate visualization of the myoma during less than half of the procedure despite continuous and constant irrigation of the distention media Good When it is possible to assess the entire uterine cavity to include the cornual areas from the level of isthmus satisfactorily throughout the entire procedure with adequate visualization of the myoma.
Measured: start with the first resectoscope myoma cut till the completion of myoma resection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2020
- Study start15 Jul 2020
- Primary completion30 Dec 2021
- Study completion1 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Myoma;UterusStudies 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized controlled trial (RCT).
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mansoura University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohamed Taman, Mansoura University Hospital
- Investigators
- Mohamed E Taman, MD, Principal investigator, Faculty of Medicine - Mansoura University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04482959
- Sponsor's protocol ID
- MS.20.07.1178
- Status last verified
- Apr 2022
- First submitted
- 19 Jul 2020
- Last updated
- 6 Apr 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Neuwirth RS, Amin HK. Excision of submucus fibroids with hysteroscopic control. Am J Obstet Gynecol. 1976 Sep 1;126(1):95-9. doi: 10.1016/0002-9378(76)90471-3.
PubMed 961753Di Spiezio Sardo A, Mazzon I, Bramante S, Bettocchi S, Bifulco G, Guida M, Nappi C. Hysteroscopic myomectomy: a comprehensive review of surgical techniques. Hum Reprod Update. 2008 Mar-Apr;14(2):101-19. doi: 10.1093/humupd/dmm041. Epub 2007 Dec 6.
PubMed 18063608Deutsch A, Sasaki KJ, Cholkeri-Singh A. Resectoscopic Surgery for Polyps and Myomas: A Review of the Literature. J Minim Invasive Gynecol. 2017 Nov-Dec;24(7):1104-1110. doi: 10.1016/j.jmig.2017.08.645. Epub 2017 Aug 24.
PubMed 28843536Malm M, Madsen I, Kjellstrom J. Development and stability of a heat-stable formulation of carbetocin for the prevention of postpartum haemorrhage for use in low and middle-income countries. J Pept Sci. 2018 Jun;24(6):e3082. doi: 10.1002/psc.3082. Epub 2018 Apr 27.
PubMed 29700898Munro MG, Critchley HO, Broder MS, Fraser IS; FIGO Working Group on Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011 Apr;113(1):3-13. doi: 10.1016/j.ijgo.2010.11.011. Epub 2011 Feb 22.
PubMed 21345435
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intraoperative Carbetocin to Decrease Blood Loss During Hysteroscopic Myomectomy: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04482959
- Acronym / sponsor ID
- MS.20.07.1178
- Conditions
- Myoma;Uterus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Mansoura University HospitalUniversity, hospital or other
- Study start
- 15 Jul 2020 (actual)
- Primary completion
- 30 Dec 2021 (actual)
- Study completion
- 1 Feb 2022 (actual)
- First posted
- 23 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Submucous myomas represent one of the main indications of operative hysteroscopy. Since 1976 when Neuwirth and Amin reported the first five cases of excision of submucous myomas , several techniques have been developed in order to render hysteroscopic myomectomy a safe and effective procedure .
Hysteroscopic myomectomy is currently considered the "gold standard" minimally invasive approach for the treatment of symptomatic submucous myomas . Patients undergoing hysteroscopic myomectomy are liable to significant blood loss, and hemodynamic and hematological disturbances. Excessive bleeding during hysteroscopic myomectomy remains a major challenge for the endoscopic gynecological surgeons. Many interventions were introduced to reduce the risk of bleeding during myomectomy. These include the use of utero-tonics such as oxytocin, or the use of anti-fibrinolytics such as tranexamic acid . The potential advantage of oxytocin infusion during hysteroscopic myomectomy is that it can maintains uterine contractility throughout the procedure, and thus, reduce blood loss .
Carbetocin (1-deamino-1-monocarba-(0-2-methyltyrosine)-oxytocin) is a long-acting synthetic agonist analogue of the human oxytocin. When injected to a woman, it induces uterine contractions . Although many interventions have been described to reduce the intraoperative blood loss during hysteroscopic myomectomy, there is a need for a well-designed randomized controlled trials to identify the most efficient interventions, with reasonable safety profiles, to help the perform a safe and curative surgery.
Detailed description
All patients will have preoperative evaluation by gynecologists and anesthetists, with history taking and pelvic examination. A TVS scan will be done to determine the number, size and location of the myomas, and evaluate the myometrial free margin (the minimum thickness between the outer edge of the myoma and inner edge of the uterine serosa), which was found to be ideally ≥ 10 mm (11). Prior office diagnostic hysteroscopy will be performed for evaluation of the number, location and grade of the submucous myomas, and assessment of the endocervical canal and uterine cavity and the position of the tubal ostia in order to aid orientation. Preoperative full blood count, serum creatinine, fasting blood glucose, liver enzymes, coagulation profile ( INR), and viral markers will be done for all the patients. Monopolar resectoscopic myomectomies will be scheduled in the proliferative phase of menstrual cycle by a single experienced operator.
After induction of general anesthesia, immediately before the operation, participants will receive either 1 ml of carbetocin (100 mcg/ml) IV over 1 minute (study group) or 1 ml of sodium chloride 0.9% IV over 1 minute (control group). The procedure will be done using the available standard setup and the distending solution used will be 1.5% glycine. A drape with a fluid-collection pouch (Lingeman 3 in 1 Procedure Drape, Lingeman Medical Products, Inc., Indianapolis, IN) placed beneath the woman's buttocks will be used to collect outflow fluid escaping between the cervix and sheath to prevent spillage of irrigating fluid onto the floor. Fluid inflow and outflow will be monitored every 3-5 minutes. The outflow fluid will be measured to the nearest milliliter. The inflow and outflow volumes of the distension solution will be carefully monitored continuously during the procedure by nurses not involved in the study under the current monitoring protocol at the operating theater. The procedure would be terminated if the fluid imbalance reached 1 L.
After completing the procedure, the surgeon completed a record sheet for rating of bleeding amount and the quality of operative view. Postoperative full blood count will be done for all patients 24 hours after the procedures. Preoperative and postoperative hemoglobin and hematocrit, the need for blood transfusion, the duration of operation, any operative complications and medication adverse effects will be recorded.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Randomized controlled trial (RCT).
| Arm | Type | Receives |
|---|---|---|
| Carbetocin group | Experimental | Drug: CarbetocinThis group will contain 20 patients having single type 0 or I submucous uterine myomas according to International Federation of Gynecology and Obstetrics classification system with a largest diameter ≤ 4 cm and myometrial free margin of at least 10 mm.After induction of general anesthesia, immediately before the operation, participants will receive either 1 ml of carbetocin (100 mcg/ml) IV over 1 minute. |
| • Control group | Placebo comparator | Drug: Sodium chloride 0.9%This group will contain 20 patients having single type 0 or I submucous uterine myomas according to International Federation of Gynecology and Obstetrics classification system with a largest diameter ≤ 4 cm and myometrial free margin of at least 10 mm.After induction of general anesthesia, immediately before the operation, participants will receive either 1 ml of sodium chloride 0.9% IV over 1 minute. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Symptomatic women aged 18-45 years diagnosed by transvaginal sonography (TVS) to have single type 0 or I submucous uterine myomas according to FIGO classification system with a largest diameter ≤ 4 cm and myometrial free margin of at least 10 mm.
Key exclusion criteria (9 listed)
- • Age < 18 or > 45 years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Carbetocin(1-deamino-1-monocarba-(0-2-methyltyrosine)-oxytocin) is a long-acting synthetic agonist analogue of the human oxytocin | Drug | Carbetocin group |
| Sodium chloride 0.9%Physiological solution will be used as placebo | Drug | • Control group |
Primary outcome
intraoperative bleeding amount
Time frame: Time Frame: Start with the first resectoscope myoma cut till withdrawal of hysteroscope through the cervix at the end of the procedure
Minimal Bleeding is insufficient to interfere with the operation or with the clarity of vision Moderate Bleeding that obscure the visual field and resolves only with continuous and constant irrigation of the distention media Excessive Bleeding that necessitate intervention other than continuous and constant irrigation of the distention media (e.g. controlled only by increasing the pressure to tamponade the bleeding from myoma bed)
• Change in haemoglobin and hematocrit
Time frame: Haemoglobin and hematocrit values 24 hours before myomectomy and 24 hour after myomectomy
• Change in haemoglobin and hematocrit as surrogate measures of haemostatic effect
3 secondary outcomes
• Operative time
Time frame: Start with insertion of hysteroscope through the cervix ends with withdrawal of hysteroscopy through the cervix at the end of the procedure
• Fluid deficit
Time frame: start with insertion of hysteroscope through the cervix ends with withdrawal of hysteroscopy through the cervix at the end pf the procedure
• The quality of operative view
Time frame: start with the first resectoscope myoma cut till the completion of myoma resection
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2022.
- Results publication: PubMed 961753Neuwirth RS, Amin HK. Excision of submucus fibroids with hysteroscopic control. Am J Obstet Gynecol. 1976 Sep 1;126(1):95-9. doi: 10.1016/0002-9378(76)90471-3.
- Results publication: PubMed 18063608Di Spiezio Sardo A, Mazzon I, Bramante S, Bettocchi S, Bifulco G, Guida M, Nappi C. Hysteroscopic myomectomy: a comprehensive review of surgical techniques. Hum Reprod Update. 2008 Mar-Apr;14(2):101-19. doi: 10.1093/humupd/dmm041. Epub 2007 Dec 6.
- Results publication: PubMed 28843536Deutsch A, Sasaki KJ, Cholkeri-Singh A. Resectoscopic Surgery for Polyps and Myomas: A Review of the Literature. J Minim Invasive Gynecol. 2017 Nov-Dec;24(7):1104-1110. doi: 10.1016/j.jmig.2017.08.645. Epub 2017 Aug 24.
- Results publication: PubMed 29700898Malm M, Madsen I, Kjellstrom J. Development and stability of a heat-stable formulation of carbetocin for the prevention of postpartum haemorrhage for use in low and middle-income countries. J Pept Sci. 2018 Jun;24(6):e3082. doi: 10.1002/psc.3082. Epub 2018 Apr 27.
- Results publication: PubMed 21345435Munro MG, Critchley HO, Broder MS, Fraser IS; FIGO Working Group on Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011 Apr;113(1):3-13. doi: 10.1016/j.ijgo.2010.11.011. Epub 2011 Feb 22.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mohamed E Taman, MD principal investigator
Faculty of Medicine - Mansoura University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Carbetocin and Sodium chloride 0.9% in people with Myoma;Uterus, run by Mansoura University Hospital at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
intraoperative bleeding amount (time frame: Time Frame: Start with the first resectoscope myoma cut till withdrawal of hysteroscope through the cervix at the end of the procedure). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04482959, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2022.