Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202405917242393 Date of Approval: 24/05/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Use of preoperative sodium bicarbonate among women with obstructed labor (SoBicOL- II)
Official scientific title Effectiveness and Safety Dosing of Sodium Bicarbonate in Women with Obstructed Labor in Eastern Uganda: A Phase III Randomized placebo-controlled Trial (SoBicOL- II Study)
Brief summary describing the background and objectives of the trial Oral bicarbonate is a safe, cheap and effective acid buffer, widely used in sports to improve performance because of its ability to prevent and reverse the effects of metabolic acidosis. Clinically, it is used in intensive care to treat patients with overwhelming infections or poisoning. In low resource settings, obstructed labor (OL) is a major problem and accounts for 22% of maternal deaths. The fetal harm of OL comes from intrapartum asphyxia, characterized by accumulation of hydrogen ions that cross the placental barrier to cause fetal acidosis. Acidosis causes failure of basic cellular functions resulting into cell death. In a recent RCT, we found that 61% of 477 women with OL were acidotic (lactate >4.8 mmol/L) and a median capillary blood lactate level of 6.9 (3.4–13) mmol/L. A potential way of improving maternal and perinatal outcomes among women with OL would be to buffer the excess lactic acid with sodium bicarbonate, achieving intrauterine resuscitation whilst awaiting an emergency cesarean section. However, in this situation, there is inadequate time (or staff) to correct the acidaemia through careful titration of the bicarbonate infusion. A universal safe and effective dose would therefore facilitate its use. In our previous RCT, a single dose of 4.2g was insufficient to achieve changes in maternal or neonatal lactate levels. It is not known if a higher dose of bicarbonate would reverse the acidosis and achieve clinical benefits for the mother and baby. Objectives General objective To determine the efficacy and safety of a preoperative infusion of sodium bicarbonate on lactate levels (metabolic acidosis) among women with obstructed labour. Specific objectives To determine the efficacy of a preoperative infusion of sodium bicarbonate on acidosis, compared with placebo among women with obstructed labour (OL). To determine the safety of a preoperative infusion of sodium bicarbonate on acidosis, compared with placebo among women with obstructed labour (OL).
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Pregnancy and Childbirth
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/08/2024
Actual trial start date
Anticipated date of last follow up 31/07/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 280
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
BUFHS2024164 Busitema University Faculty of Health Sciences Research and Ethics Committee
CTA0267 Uganda National Drug Authority
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Numbered containers Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Sodium bicarbonate solution Eligible participants will be randomly assigned to receive 100 mls (8.4g), 150mls (12.6g) and 200 mls (16.8g) of 8.4% sodium bicarbonate solution. Each participant will receive up to two doses of the same strength solution (regimen), with four hours apart. Each participant will receive up to two doses of the same strength solution (regimen) preoperatively, with four hours apart. However, since the average waiting time for caesarean section in our labour ward is approximately 110 minutes, there may be no need for a repeat dose because this is only indicated after 4 hours from the previous dose. Sodium bicarbonate infusion 8.4% solution The study drug will be contained in identical 25 mL glass vials (Neon Laboratories Ltd, Mumbai, India), administered intravenously as a single bolus dose. 210
Control Group Normal Saline Participants randomized to the control group will receive 50 mls of Normal Saline 0.9%. Each participant will receive up to two doses of the same strength solution (regimen) preoperatively, four hours apart. Participants will receive up to two doses of the same strength solution (regimen) preoperatively, four hours apart. However, since the average waiting time for caesarean section in our labour ward is approximately 110 minutes, there may be no need for a repeat dose because this is only indicated after 4 hours from the previous dose. 50 mls of Normal Saline 0.9% 70 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
We will include patients with obstructed labour carrying singleton, term pregnancies (≥37 weeks of gestation) in cephalic presentation. We will exclude patients with other obstetric emergencies such as antepartum haemorrhage, preeclampsia and eclampsia (defined as elevated blood pressure of at least 140/90 mm Hg, urine protein of at least 2+, any of the danger signs and fits), premature rupture of membranes and intrauterine fetal death. Patients with comorbidities such as diabetes mellitus, sickle cell disease, renal disease, liver disease and heart disease. We will also exclude those patients with hypokalaemia (148 mmol/L) and alkalosis (bicarbonate >22 mmol/L) because they are more likely to develop adverse drug reactions Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year 16 Year(s) 45 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 14/03/2024 Busitema University Faculty of Health Sciences Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Mbale Mbale City 256 Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The primary outcome measure will be the mean change in maternal pH from baseline in each group. In umbilical blood it will be the mean pH in each arm of the study At baseline, 30, 60, 90, 120 and 150 minutes
Secondary Outcome The secondary outcomes will include mean lactate in maternal and umbilical blood, early neonatal death, safety (side effects) of sodium bicarbonate, primary postpartum hemorrhage, sepsis and death. Furthermore, the plasma concentrations of bicarbonate levels will be measured as well to accurately estimate the required dose. Bicarbonate concentrations will be measured at baseline, 30, 60, 90, 120, 150 and at birth. Maternal and Umbilical cord blood lactate will be measured at baseline and at birth.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Mbale regional referral hospital Mbale Mbale city 256 Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
Cures Within Reach and Open Philanthropy GV673603676 Howard Street Chicago United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Busitema University Mbale Mbale Uganda University
COLLABORATORS
Name Street address City Postal code Country
Trond Michelsen Sognsvannsveien Oslo Norway
Andrew D Weeks Brownlow Hill Liverpool United Kingdom
David Mukunya Mbale Mbale Uganda
Julius N Wandabwa Mbale Mbale Uganda
Mugabe Kenneth Mbale Mbale Uganda
Dan Kibuule Mbale Mbale Uganda
Milton Musaba Mbale Mbale Uganda
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Milton Musaba ritahclaire24@gmail.com 256704913791 Mbale
City Postal code Country Position/Affiliation
Mbale Uganda Associate Professor of Obstetrics and Gynaecology Busitema University Uganda
Role Name Email Phone Street address
Public Enquiries Ritah Nantale ritahclaire24@gmail.com 256702035356 Mbale
City Postal code Country Position/Affiliation
Mbale Uganda Research Manager
Role Name Email Phone Street address
Scientific Enquiries Milton Musaba miltonmusaba@gmail.com 256704913791 Mbale
City Postal code Country Position/Affiliation
Mbale Uganda Associate Professor of Obstetrics and Gynaecology Busitema University Uganda
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be freely available. Analytic Code,Statistical Analysis Plan,Study Protocol Immediately following publication, No end date Anyone who wishes to access the data. Any types of data analyses will be permitted.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information