Placenta PreviaPhase 4NCT05340205
Blood Loss During Cesarean Delivery in Placenta Previa Patients
A Phase 4 study testing Tranexamic acid, Misoprostol and Oxytocin in people with Placenta Previa, run by Cairo University at 1 site in Egypt.
Trial summary
To compare the efficacy and safety profile of intravenous tranexamic acid versus intrauterine misoprostol in reducing the blood loss during and after cesarean delivery in pregnant women diagnosed with placenta previa Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Placenta Previa
- What is being tested?
- Tranexamic acid, Misoprostol and Oxytocin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 1 siteEgypt
- Study dates
- 4 May 2022to 5 Jan 2023
- 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 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Parity: primigravida or multigravida.
- Gestational age: ≥ 36 weeks (confirmed by the first day of the last menstrual period or first trimester ultrasound scan).
- Candidate for termination of pregnancy by cesarean delivery.
- Singleton living healthy normally growing fetus.
- Cesarean delivery under spinal anesthesia.
- Pregnancies complicated with placenta previa diagnosed preoperatively by ultrasonography (placenta previa was defined as placenta partially or totally covers the cervix)
Who cannot join
- Patients diagnosed with morbidly adherent placenta.
- Placenta previa cases requiring cesarean hysterectomy in the primary surgery.
- Patients with preoperative anemia (Hemoglobin <9 gm/dl).
- History of thromboembolic event.
- Known allergy to tranexamic acid or prostaglandins.
- Bronchial asthma or other contraindications of misoprostol.
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- Patients with other risk factors of postpartum hemorrhage (e.g., polyhydramnios, fetal macrosomia, uterine fibroid).
- Patients known to have bleeding tendency (e.g., those receiving anticoagulation, patients with thrombocytopenia, factor VIII or IX deficiency or Von Willebrand's disease).
- More than 2 previous cesarean deliveries procedures.
- Prolonged procedure (more than 2 hours from skin incision to skin closure).
- Concomitant maternal medical disorders (either chronic or pregnancy induced)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Efficacy and Safety of Intrauterine Misoprostol Versus Intravenous Tranexamic Acid in Reducing Blood Loss During and After Cesarean Delivery in Patients With Placenta Previa: A Randomized Controlled Trial
To compare the efficacy and safety profile of intravenous tranexamic acid versus intrauterine misoprostol in reducing the blood loss during and after cesarean delivery in pregnant women diagnosed with placenta previa
Read the detailed description
Placenta previa is defined as complete or partial covering of the internal os of the cervix with the placenta, at more than 16 weeks of gestation. It affects 0.3% to 2% of pregnancies in the third trimester and has become more evident secondary to the increasing rates of cesarean delivery (CD).
Placenta previa is a major risk factor for postpartum hemorrhage (PPH) and can lead to maternal and neonatal morbidity and mortality. Uncontrolled PPH from placenta previa may necessitate blood transfusion, hysterectomy, admission to the intensive care unit, or even death.
The efficacy of routine administration of oxytocin, to reduce the frequency of PPH after vaginal and cesarean birth is well-established. The Royal College of Obstetricians and Gynecologists recommends a slow IV bolus dose of 5 IU of oxytocin after delivery of the neonate in CD to ensure adequate uterine contractility, reduce intraoperative blood loss and prevent PPH. Likewise, the American College of Obstetricians and Gynecologists recommends the practice to use oxytocin but infusion instead of a bolus dose. Regardless of the mode of administration, oxytocin use in the setting of CD may result in maternal adverse effects, such as hypotension and tachycardia.
Misoprostol, a prostaglandin E1 analogue with strong uterotonic properties binds to myometrial cells to cause strong myometrial contractions. Misoprostol has been suggested as an alternative to injectable uterotonic agents for preventing PPH following vaginal or CD. It can be used orally, sublingually, buccally, rectally or put intrauterine with similar efficacy as oxytocin in reducing blood loss, preventing and treating PPH. Because of its availability, low cost, thermal stability, and ease of administration, misoprostol is suitable for worldwide use even in low resource settings in developing countries.
Tranexamic Acid (TA) is an analogue of lysine that inhibits fibrinolysis by competitively binding to plasminogen. It prevents the lysis of formed clot by inhibiting activation of plasminogen and plasmin. It is ten times more potent than amino-caproic acid. Several studies had assessed the use of TA in both the prophylaxis against and the treatment of PPH with the conclusion that TA reduces the following; blood loss in women with PPH, the need for hysterectomy, the risk of severe anemia and the need for further blood transfusion; hence, this could contribute significantly to the goal of reducing maternal mortality
- Conditions
- Placenta Previa
- Being tested
- Tranexamic acid, Misoprostol, Oxytocin
- Medical subject headings
- Placenta Previa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tranexamic acidDrug
Also called Kapron
Patients will receive 1 gm tranexamic acid diluted in 20 ml of Glucose 5% 15 minutes prior to skin incision and a slow IV bolus of 5 IU oxytocin and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h) following delivery of the baby.
MisoprostolDrug
Also called Cytotec
Patients will receive 400 microgram misoprostol which will be inserted inside the uterus near the cornu after delivery of the placenta and a slow IV bolus of 5 IU oxytocin and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h).
.
OxytocinDrug
Also called Syntocinon
Patients will receive an IV bolus of 5 IU oxytocin and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h) following the delivery of the baby.
| Study group | Role | What they receive |
|---|---|---|
| Tranexamic acid group | Active comparator | Patients will receive 1 gm (10 ml) tranexamic acid diluted in 20 ml of Glucose 5% (administered as IV infusion over 5 minutes, at least 15 minutes prior to skin incision). Following the delivery of the baby, patients will additionally receive a slow IV bolus of 5 IU oxytocin and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h). Receives: Drug: Tranexamic acid |
| Misoprostol group | Active comparator | Patients will receive 400 microgram misoprostol which will be inserted inside the uterus near the cornu after delivery of the placenta and swabbing the uterine cavity. Patients will additionally receive a slow IV bolus of 5 IU oxytocin and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h). Receives: Drug: Misoprostol |
| Oxytocin only (control) group | Active comparator | Patients will receive only an IV bolus of 5 IU oxytocin and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h) following the delivery of the baby. Receives: Drug: Oxytocin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the estimated blood loss during cesarean delivery among the three groups
The blood loss will be estimated in each of the three groups
Measured: less than 2 hours
Secondary outcomes (5)
The Use of additional ecbolics denoting uterine atony
The need for extra ecbolics will be recorded
Measured: Baseline
The occurrence of excessive blood loss (> 1000 mL) within the first 24 hours postoperatively
Excessive blood loss will be recorded
Measured: First 24 hours postoperatively
The need for blood transfusion
The need for blood transfusion will be recorded
Measured: During cesarean delivery and the first 24 hours postoperatively
The occurrence of any maternal side effects in the studied groups
Maternal side effects will be recorded
Measured: First 6 hours postoperatively
The occurrence of any neonatal outcome in the studied groups
Neonatal side effects will be recorded
Measured: The first 6 hours postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2022
- Study start4 May 2022
- Primary completion15 Dec 2022
- Study completion5 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Placenta PreviaStudies of the same condition, open and under way.
- More trials run by Cairo UniversityThe sponsor's other registered studies.
- 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
- Masking
- None (open label)
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Noran Amin, Cairo University
- Investigators
- Tarek El Husseiny, MD, Study director, Cairo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05340205
- Sponsor's protocol ID
- Placenta previa disorders
- Status last verified
- Jan 2023
- First submitted
- 11 Apr 2022
- Last updated
- 6 Jan 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Bhattacharya S, Ghosh S, Ray D, Mallik S, Laha A. Oxytocin administration during cesarean delivery: Randomized controlled trial to compare intravenous bolus with intravenous infusion regimen. J Anaesthesiol Clin Pharmacol. 2013 Jan;29(1):32-5. doi: 10.4103/0970-9185.105790.
PubMed 23493050Martinelli KG, Garcia EM, Santos Neto ETD, Gama SGND. Advanced maternal age and its association with placenta praevia and placental abruption: a meta-analysis. Cad Saude Publica. 2018 Feb 19;34(2):e00206116. doi: 10.1590/0102-311X00206116.
PubMed 29489954Prata N, Weidert K. Efficacy of misoprostol for the treatment of postpartum hemorrhage: current knowledge and implications for health care planning. Int J Womens Health. 2016 Jul 29;8:341-9. doi: 10.2147/IJWH.S89315. eCollection 2016.
PubMed 27536161Pabinger I, Fries D, Schochl H, Streif W, Toller W. Tranexamic acid for treatment and prophylaxis of bleeding and hyperfibrinolysis. Wien Klin Wochenschr. 2017 May;129(9-10):303-316. doi: 10.1007/s00508-017-1194-y. Epub 2017 Apr 21.
PubMed 28432428Sood AK, Singh S. Sublingual misoprostol to reduce blood loss at cesarean delivery. J Obstet Gynaecol India. 2012 Apr;62(2):162-7. doi: 10.1007/s13224-012-0168-2. Epub 2012 Jun 1.
PubMed 23543254Vogel JP, West HM, Dowswell T. Titrated oral misoprostol for augmenting labour to improve maternal and neonatal outcomes. Cochrane Database Syst Rev. 2013 Sep 23;2013(9):CD010648. doi: 10.1002/14651858.CD010648.pub2.
PubMed 24058051Della Corte L, Saccone G, Locci M, Carbone L, Raffone A, Giampaolino P, Ciardulli A, Berghella V, Zullo F. Tranexamic acid for treatment of primary postpartum hemorrhage after vaginal delivery: a systematic review and meta-analysis of randomized controlled trials. J Matern Fetal Neonatal Med. 2020 Mar;33(5):869-874. doi: 10.1080/14767058.2018.1500544. Epub 2018 Sep 10.
PubMed 30122082
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy and Safety of Intrauterine Misoprostol Versus Intravenous Tranexamic Acid in Reducing Blood Loss During and After Cesarean Delivery in Patients With Placenta Previa: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05340205
- Acronym / sponsor ID
- Placenta previa disorders
- Conditions
- Placenta Previa
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Study start
- 4 May 2022 (actual)
- Primary completion
- 15 Dec 2022 (actual)
- Study completion
- 5 Jan 2023 (actual)
- First posted
- 22 Apr 2022 (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.
To compare the efficacy and safety profile of intravenous tranexamic acid versus intrauterine misoprostol in reducing the blood loss during and after cesarean delivery in pregnant women diagnosed with placenta previa
Detailed description
Placenta previa is defined as complete or partial covering of the internal os of the cervix with the placenta, at more than 16 weeks of gestation. It affects 0.3% to 2% of pregnancies in the third trimester and has become more evident secondary to the increasing rates of cesarean delivery (CD).
Placenta previa is a major risk factor for postpartum hemorrhage (PPH) and can lead to maternal and neonatal morbidity and mortality. Uncontrolled PPH from placenta previa may necessitate blood transfusion, hysterectomy, admission to the intensive care unit, or even death.
The efficacy of routine administration of oxytocin, to reduce the frequency of PPH after vaginal and cesarean birth is well-established. The Royal College of Obstetricians and Gynecologists recommends a slow IV bolus dose of 5 IU of oxytocin after delivery of the neonate in CD to ensure adequate uterine contractility, reduce intraoperative blood loss and prevent PPH. Likewise, the American College of Obstetricians and Gynecologists recommends the practice to use oxytocin but infusion instead of a bolus dose. Regardless of the mode of administration, oxytocin use in the setting of CD may result in maternal adverse effects, such as hypotension and tachycardia.
Misoprostol, a prostaglandin E1 analogue with strong uterotonic properties binds to myometrial cells to cause strong myometrial contractions. Misoprostol has been suggested as an alternative to injectable uterotonic agents for preventing PPH following vaginal or CD. It can be used orally, sublingually, buccally, rectally or put intrauterine with similar efficacy as oxytocin in reducing blood loss, preventing and treating PPH. Because of its availability, low cost, thermal stability, and ease of administration, misoprostol is suitable for worldwide use even in low resource settings in developing countries.
Tranexamic Acid (TA) is an analogue of lysine that inhibits fibrinolysis by competitively binding to plasminogen. It prevents the lysis of formed clot by inhibiting activation of plasminogen and plasmin. It is ten times more potent than amino-caproic acid. Several studies had assessed the use of TA in both the prophylaxis against and the treatment of PPH with the conclusion that TA reduces the following; blood loss in women with PPH, the need for hysterectomy, the risk of severe anemia and the need for further blood transfusion; hence, this could contribute significantly to the goal of reducing maternal mortality
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tranexamic acid group | Active comparator | Drug: Tranexamic acidPatients will receive 1 gm (10 ml) tranexamic acid diluted in 20 ml of Glucose 5% (administered as IV infusion over 5 minutes, at least 15 minutes prior to skin incision). Following the delivery of the baby, patients will additionally receive a slow IV bolus of 5 IU oxytocin and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h). |
| Misoprostol group | Active comparator | Drug: MisoprostolPatients will receive 400 microgram misoprostol which will be inserted inside the uterus near the cornu after delivery of the placenta and swabbing the uterine cavity. Patients will additionally receive a slow IV bolus of 5 IU oxytocin and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h). |
| Oxytocin only (control) group | Active comparator | Drug: OxytocinPatients will receive only an IV bolus of 5 IU oxytocin and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h) following the delivery of the baby. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Parity: primigravida or multigravida.
- Gestational age: ≥ 36 weeks (confirmed by the first day of the last menstrual period or first trimester ultrasound scan).
- Candidate for termination of pregnancy by cesarean delivery.
- Singleton living healthy normally growing fetus.
- Cesarean delivery under spinal anesthesia.
Key exclusion criteria (11 listed)
- Patients diagnosed with morbidly adherent placenta.
- Placenta previa cases requiring cesarean hysterectomy in the primary surgery.
- Patients with preoperative anemia (Hemoglobin <9 gm/dl).
- History of thromboembolic event.
- Known allergy to tranexamic acid or prostaglandins.
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 |
|---|---|---|
| Tranexamic acidAlso: KapronPatients will receive 1 gm tranexamic acid diluted in 20 ml of Glucose 5% 15 minutes prior to skin incision and a slow IV bolus of 5 IU oxytocin and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h) following delivery of the baby. | Drug | Tranexamic acid group |
| MisoprostolAlso: CytotecPatients will receive 400 microgram misoprostol which will be inserted inside the uterus near the cornu after delivery of the placenta and a slow IV bolus of 5 IU oxytocin and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h). . | Drug | Misoprostol group |
| OxytocinAlso: SyntocinonPatients will receive an IV bolus of 5 IU oxytocin and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h) following the delivery of the baby. | Drug | Oxytocin only (control) group |
Primary outcome
To compare the estimated blood loss during cesarean delivery among the three groups
Time frame: less than 2 hours
The blood loss will be estimated in each of the three groups
5 secondary outcomes
The Use of additional ecbolics denoting uterine atony
Time frame: Baseline
The occurrence of excessive blood loss (> 1000 mL) within the first 24 hours postoperatively
Time frame: First 24 hours postoperatively
The need for blood transfusion
Time frame: During cesarean delivery and the first 24 hours postoperatively
The occurrence of any maternal side effects in the studied groups
Time frame: First 6 hours postoperatively
The occurrence of any neonatal outcome in the studied groups
Time frame: The first 6 hours postoperatively
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 Jan 2023.
- Background: PubMed 23493050Bhattacharya S, Ghosh S, Ray D, Mallik S, Laha A. Oxytocin administration during cesarean delivery: Randomized controlled trial to compare intravenous bolus with intravenous infusion regimen. J Anaesthesiol Clin Pharmacol. 2013 Jan;29(1):32-5. doi: 10.4103/0970-9185.105790.
- Background: PubMed 29489954Martinelli KG, Garcia EM, Santos Neto ETD, Gama SGND. Advanced maternal age and its association with placenta praevia and placental abruption: a meta-analysis. Cad Saude Publica. 2018 Feb 19;34(2):e00206116. doi: 10.1590/0102-311X00206116.
- Background: PubMed 27536161Prata N, Weidert K. Efficacy of misoprostol for the treatment of postpartum hemorrhage: current knowledge and implications for health care planning. Int J Womens Health. 2016 Jul 29;8:341-9. doi: 10.2147/IJWH.S89315. eCollection 2016.
- Background: PubMed 28432428Pabinger I, Fries D, Schochl H, Streif W, Toller W. Tranexamic acid for treatment and prophylaxis of bleeding and hyperfibrinolysis. Wien Klin Wochenschr. 2017 May;129(9-10):303-316. doi: 10.1007/s00508-017-1194-y. Epub 2017 Apr 21.
- Background: PubMed 23543254Sood AK, Singh S. Sublingual misoprostol to reduce blood loss at cesarean delivery. J Obstet Gynaecol India. 2012 Apr;62(2):162-7. doi: 10.1007/s13224-012-0168-2. Epub 2012 Jun 1.
- Background: PubMed 24058051Vogel JP, West HM, Dowswell T. Titrated oral misoprostol for augmenting labour to improve maternal and neonatal outcomes. Cochrane Database Syst Rev. 2013 Sep 23;2013(9):CD010648. doi: 10.1002/14651858.CD010648.pub2.
- Background: PubMed 30122082Della Corte L, Saccone G, Locci M, Carbone L, Raffone A, Giampaolino P, Ciardulli A, Berghella V, Zullo F. Tranexamic acid for treatment of primary postpartum hemorrhage after vaginal delivery: a systematic review and meta-analysis of randomized controlled trials. J Matern Fetal Neonatal Med. 2020 Mar;33(5):869-874. doi: 10.1080/14767058.2018.1500544. Epub 2018 Sep 10.
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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.
Tarek El Husseiny, MD study director
Cairo 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 Tranexamic acid, Misoprostol and Oxytocin in people with Placenta Previa, run by Cairo University 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 6 inclusion and 11 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 Jan 2023. 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. 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?
To compare the estimated blood loss during cesarean delivery among the three groups (time frame: less than 2 hours). 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 NCT05340205, which also lists 7 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 Jan 2023.