Intravenous Nitroglycerin for Retained Placenta Extraction: a Multicenter Study
Primary objective The primary objective of this study is to see whether intravenous (IV) NTG 100-200 microgram can effectively help extract retained placenta as compared to placebo, in a randomized controlled multicenter study.
Secondary objective is to compare the hypotensive effects of NTG as compared to placebo, including others side effects such as headache, blood loss, or others.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Intravenous Nitroglycerin for Retained Placenta Extraction: a Multicenter Study|
- successful of placenta extraction [ Time Frame: 5 mintues ] [ Designated as safety issue: Yes ]
- hypotension [ Time Frame: 20 mintues ] [ Designated as safety issue: Yes ]
- headache [ Time Frame: 2 hour ] [ Designated as safety issue: Yes ]
- blood loss [ Time Frame: 24 hour ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2008|
|Study Completion Date:||December 2010|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Active Comparator: 1
1=nitroglycerine 100 microgram intravenous100-200 microgram of IV.
nitroglycerine 100 microgram intravenous.Once the placenta had been delivered, oxytocin or ergometrine will be administered. Fentanyl 50-100 microgram can be given if the cord traction is considered painful.
Other Name: trinitroglycerin,trinitroglycerine,glyceryl trinitrate
Placebo Comparator: 2
2=placebo with the same volume as NTG 100-200 microgram of IV.
NSS.Once the placenta had been delivered, oxytocin or ergometrine will be administered. Fentanyl 50-100 microgram can be given if the cord traction is considered painful.
Other Name: normal saline
After the approval of the Ethical committee of each institute, and consent signed by the patient, 100 patients with retained placenta were divided into 2 groups in 5 tertiary care centers, university hospitals. By using the program research randomizer (from www. Randomizer.org/form.htm), with the block of 10 and the numbers within the concealed envelopes, totally 100 patients with retained placenta will be divided into 2 groups to have either 100-200 microgram of IV, NTG or IV placebo. Due to unequal number of the cases enrolled in each centers, they will receive 10 envelopes for 10 cases (5 NTG and 5 placebo) at a time. When they finish the first 10 cases, they will start another 10 cases of the next set until all 10 sets has been started. Each of 5 centers might enroll the cases between 10 to 40 cases up to their populations..
Once a diagnosis of retained placenta has been made ( ≥ 30 min after delivery), Hematocrit will be checked and IV crystalloid solution 500 ml has been rapidly perfuse and noninvasive monitored included pulse oximetry, electrocardiogram and noninvasive blood pressure will be monitored.
Patients with signs of hypovolemia ( SBP < 100 mmHg, or pulse > 100/min), or ASA classification > II will be excluded from the study.
First step: In the treatment group, 100 microgram of NTG will be given and wait for 80 seconds ( maximum relaxation effects of IV NTG)(5,6) before starting gently cord traction (1min). If the placenta can not be extracted, another 100 microgram NTG from the same syringe will be given and wait for another 80 seconds before starting another extraction (1min), If the placenta can not be extracted, it will be considered failed. In the placebo group, NSS will be used instead of NTG.
Second step: To give a chance for patients in placebo group, another syringe with 200 microgram will be given as in the first step for the placebo group. In the treatment group, NSS will be used instead of NTG. The outcome in the second step will not be included in the first step.( The solutions in both syringes which will be prepared by the research assistant who will not involve in the study, will be blinded to the patient, the obstetrician, the anesthesiologist and the investigator) General anesthesia will be used for manual removal of placenta in cases that placenta can not be extracted after the second step.
Once the placenta had been delivered, oxytocin or ergometrine will be administered. Fentanyl 50-100 microgram can be given if the cord traction is considered painful.
Vital signs will be recorded before the first NTG bolus and thereafter at 1 min interval for 5 min then every 2 min for 10 min then every 5 min. for 20 min(see the CRF).
The patient will be followed up closely for 24 h postoperatively and Hct will be checked , including the final results upon discharge home.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00707928
|Department of Anesthesiology, Faculty of Medicine, Siriraj Hospital|
|Bangkok, Thailand, 10700|
|Principal Investigator:||Shusee Visalyaputra, MD||Department of Anesthesiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700|