Prevention of Postpartum Hemorrhage in Patients With Severe Preeclampsia Using Carbetocin Versus Misoprostol (carbetocin)

Carbetocin in Preventing Postpartum Bleeding in Women With Severe Preeclampsia.

We aim to compare carbetocin with misoprostol for the prevention of postpartum hemorrhage in patients with severe preeclampsia. The primary outcome is postpartum haemorrhage (blood loss of ≥ 500 ml) while our Secondary outcomes include use of additional uterotonics, need for blood transfusion, maternal adverse drug reaction, maternal complications and maternal death

Study Overview

• Status: Completed
• Conditions: Severe Pre-eclampsia, Postpartum Condition or Complication
• Intervention / Treatment: Drug: carbetocin; Drug: misoprostol

Detailed Description

We conducted a prospective non-randomized study at Department of Obstetrics and Gynecology, Benha University Hospital, since March 2013 till June 2015, after approval of the study protocol by the Local Ethical Committee. A written informed consent was obtained from eligible women before induction or at early stage of labour.

Women with singleton pregnancies of more than 28 weeks' gestation who are admitted to hospital with severe preeclampsia and candidates for vaginal delivery were eligible for the study. Preeclampsia is labelled as severe in the presence of any of the following abnormalities.

1. Persistent cerebral or visual disturbances or cerebral edema.
2. Persistent epigastric pain with nausea or vomiting, or both.
3. Systolic ≥160 mmHg or diastolic ≥110 mmHg on 2 occasions at least 6 h apart with the patient at bed rest.
4. Proteinuria of ≥5 g on 24-hour urine collection. Urine dipsticks are not accurate for this purpose.
5. Oliguria (˂500 mL in 24 hours).
6. Pulmonary edema.
7. Thrombocytopenia.

Our exclusion criteria are HELLP syndrome, eclampsia, abruptio placentae, malpresentation, polyhydramnios, previous uterine scar, chorioamnionitis and multiple pregnancies. All patients were in stable condition (no evidence of maternal hemodynamic instability or fetal distress) and their management afterwards followed the standards accepted in our country and established guidelines for the management of hypertensive disorders of pregnancy. For hypertensive crisis the first drug used was hydralazine (5 mg IV every 15 minutes to a maximum total dose of 20 mg) and, if this was ineffective, Nifedipine (Epilat): 10 to 20 mg orally / 30 min (max 50 mg), Then 10-20 mg /4-6 h (max 120 mg/day) or labetalol (20 mg IV every 10 minutes to a maximum total dose of 300 mg). No patient needed additional treatment for their symptoms or developed antepartum complications that required admission to the intensive care unit. All patients were evaluated hourly and received magnesium sulphate to prevent eclampsia during the pregnancy and for a minimum of 24 hours postpartum.

The patients (60) were divided into two groups, Group A (30) received a single dose of carbetocin (100 μg in 1 mL ampoule, Pabal) while Group B (30) received misoprostol (600 μg, 3 tables) sublingually after the delivery of the anterior shoulder of the baby.

The third stage of labour is managed as usual by clamping and cutting of umbilical cord, waiting for signs of placental separation and delivering the placenta by controlled cord traction.

Duration of the 3rd stage of labour is calculated. Patient is kept in labor room under observation for a period of 1 h and any complaint such as nausea, vomiting, fever, headache, chills, diarrhoea and shivering is noted. In cases of uterine atony (determined by physical examination and continuous postpartum bleeding) uterus is massaged and additional uterotonics were given and noted (oxytocin and/or prostaglandin, at the discretion of the attending physician). Any requirement for manual removal of the placenta or blood transfusion is also recorded.

The following laboratory assessments (hemoglobin, hematocrit, platelets, and renal and liver function tests) are performed in every patient on admission and postpartum. Vital signs (blood pressure, heart rate, respiratory rate) and urine output are measured every hour until at least 24 hours after delivery.

Measurement of blood loss A clean plastic lined absorbent drape is placed under the woman's buttocks to collect all the blood lost after delivery of the baby and drainage of the amniotic fluid. The drape is changed as many times as needed. The woman stays on the drape or asked to wear a pad over the next 60 minutes. In the case of severe haemorrhage, we follow the usual guidelines for management of postpartum haemorrhage, and the supplemental treatment is registered. All drapes and pads are weighed on an electronic scale and the known dry weight of the linen is subtracted. As 1 ml of blood weighs close to 1 g, the balance in grams is assumed to be the total blood loss in ml.

Haemoglobin concentration is measured before, 2 hours and 24 hours after delivery.

The rate of haemorrhage at labour third phase is determined by observation estimation considering the amount of blood under the patient. The rate of haemoglobin and haematocrit are measured at hospitalization and also 2 h, 24 h after delivery and then are recorded. At this interval, the patients are evaluated in terms of possible complications of administered drugs such as vomiting, diarrhoea, shivering, pyrexia, and headache).

All patients have the Foley catheter in situ for 24 hours after delivery and the amount of urine was monitored hourly.

This study has no external funding source. No author had any potential relationships that may pose conflict of interest.

Outcome measures Our primary outcome measure is postpartum haemorrhage, defined as a blood loss of ≥ 500 ml. We analyse the blood loss, change in haemoglobin concentration between admission and discharge. While secondary outcomes include use of additional uterotonics, need for blood transfusion, maternal adverse drug reaction (such as headache, vomiting, abdominal pain, pruritus, tacky or bradycardia), sever maternal complications (such as seizures or need for ICU admission) and maternal death.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Benha, Egypt, 13518
    • Benha univesity hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 42 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women with singleton pregnancies of more than 28 weeks' gestation who were admitted to hospital with severe preeclampsia and candidates for vaginal delivery were eligible for the study. Preeclampsia is labelled as severe in the presence of any of the following abnormalities:

  1. Persistent cerebral or visual disturbances or cerebral edema.
  2. Persistent epigastric pain with nausea or vomiting, or both.
  3. Systolic ≥160 mmHg or diastolic ≥110 mmHg on 2 occasions at least 6 h apart with the patient at bed rest.
  4. Proteinuria of ≥5 g on 24-hour urine collection. Urine dipsticks are not accurate for this purpose.
  5. Oliguria (˂500 mL in 24 hours).
  6. Pulmonary edema.
  7. Thrombocytopenia.

Exclusion Criteria:

• were HELLP syndrome, eclampsia, abruptio placentae, malpresentation, polyhydramnios, previous uterine scar, chorioamnionitis and multiple pregnancies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: cabetocin; a single dose of carbetocin (100 μg in 1 mL ampoule, Pabal) given intravenously after delivery of anterior shoulder	Drug: carbetocin; given after delivery of anterior shoulder; Other Names: pabal
Active Comparator: misoprostol; misoprostol (600 μg, 3 tables) sublingually after the delivery of the anterior shoulder of the baby.	Drug: misoprostol; given after the delivery of the anterior shoulder of the baby.; Other Names: cytotec; misoprost; misotec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevention of postpartum hemorrhage in patients with severe preeclampsia using carbetocin versus misoprostol	prevention of postpartum haemorrhage	24 hours after delivery

Secondary Outcome Measures

Outcome Measure	Time Frame
measurement of blood loss during second stage of labour	24 hours after delivery

Collaborators and Investigators

• Sponsor: khalid abd aziz mohamed
• Investigators: Study Chair: khalid mohamed, MD, lecturer of ob/gyn Benha faculty of medicine; Principal Investigator: ahmed sasd, MD, Lecturer; Principal Investigator: ahmed walid, Assistant profossor

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: March 5, 2014
• First Submitted That Met QC Criteria: March 9, 2014
• First Posted (Estimate): March 14, 2014

Study Record Updates

• Last Update Posted (Actual): February 15, 2017
• Last Update Submitted That Met QC Criteria: February 13, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: carbetocin, misoprostol, pre-eclampsia, pph
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Eclampsia; Pre-Eclampsia; Physiological Effects of Drugs; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Misoprostol; Carbetocin
• Other Study ID Numbers: khalid77