Effectiveness and Safety Dosing of Sodium Bicarbonate in Women With Obstructed Labor in Eastern Uganda: A Phase III Randomized Placebo-controlled Trial
Phase: PHASE3
Conditions: Obstructed Labor
Sponsor: Busitema University

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 1 of 25 
 
 
 
PROTOCOL 
Public title:  
Use of preoperative sodium bicarbonate among women with obstructed labor (SoBicOL- II). 
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)  
Sponsor: Busitema University  
Funder:  Cures Within Reach and Open Philanthropy (GV673603676) 
ReGRoW Repurposing Research for Low and Lower-Middle Income 
Countries (LMICs) 
 
 
 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 2 of 25 
Study Team 
 
Principal Investigator: 
Milton Musaba, PhD 
Associate Professor/Consultant 
Busitema University/Mbale Regional Referral Hospital, Uganda. 
miltonmusaba@gmail.com 
 
Co-Investigators: 
David Mukunya, PhD 
Epidemiologist and Biostatistician 
Busitema University, Mbale Uganda 
zebdaevid@gmail.com 
 
Trond Michelsen, PhD 
Professor/ Senior Consultant 
Oslo University Hospital Rikshospitalet, Norway 
trmi1@ous-hf.no  
 
Julius N Wandabwa, PhD 
Professor of Obstetrics and Gynaecology, 
Busitema University, Uganda 
gjwandabwa@gmail.com 
 
Mugabe Kenneth, MD 
Obstetrician & Gynaecologist 
Mbale Regional Referral Hospital 
mgbknnth@gmail.com  
 
Ritah Nantale, BSN 
Department of Community and Public Health 
 Busitema University, Uganda 
ritahclaire24@gmail.com 
 
Dan Kibuule, PhD 
Professor of Clinical Pharmacology 
Department of Pharmacology & Therapeutics 
Busitema University, Uganda 
kibuulefamily@yahoo.co.uk  
 
Andrew D Weeks, MD, MRCOG 
Professor of International Maternal Health 
Department of Women’s and Children’s Health, 
University of Liverpool, United Kingdom, 
aweeks@liv.ac.uk 
 
 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 3 of 25 
Abstract   
Introduction 
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 units to treat patients with overwhelming infections or poisoning. In low resource settings, 
obstructed labor (OL) is a major problem that 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), with 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 (pH and lactate) and achieve clinical benefits for the mother and baby.  
Methods 
An early phase III, placebo-controlled dose-ranging trial is proposed to determine the efficacy and safety of 
a pre-operative infusion of sodium bicarbonate in women with obstructed labour (OL).  In a ratio of 1:1:1: 1 
100 mls (8.4g), 150 mls (12.6g) and 200 mls (16.8g) of 8.4% sodium bicarbonate solution, or placebo (50 
mls of NS 0.9%). The primary outcome will be mean change in acidosis (pH and lactate levels) from 
baseline. The secondary outcomes will be neonatal death, safety of sodium bicarbonate, pharmacokinetics 
of sodium bicarbonate in pregnant women, primary PPH, sepsis, and maternal death.  
Conclusion 
Our results will inform the design of an effectiveness phase III trial to determine the effect of this 
preoperative infusion on maternal and perinatal outcomes. 
 
 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 4 of 25 
Introduction 
Unlike normal labour, obstructed labour is characterized by higher levels of lactic acid in maternal blood 
and amniotic fluid [1, 2]. Repetitive, prolonged, strong uterine contractions in obstructed labour impair 
oxygen supply to the placental bed which promotes anaerobic respiration and accumulation of lactic acid 
as a byproduct [3]. The accumulated lactic acid depletes the maternal and fetal buffer systems, with 
resultant metabolic acidosis [1, 3]. Without timely intervention to relieve the obstruction, coupled with 
diminishing maternal and fetal compensatory mechanisms, the accumulated hydrogen ions easily cross the 
placental barrier to cause fetal acidosis. The acidosis causes failure of basic cellular functions resulting into 
cell death. 
 Obstructed labor is a major problem that accounts for 22% of maternal deaths and 70% of perinatal 
deaths due intrapartum asphyxia in low resource settings [4].  In Uganda, half of the 26,000 perinatal 
deaths audited and reported in 2021/2022 were due to intrapartum birth asphyxia [5]. The maternal and 
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, especially if it remains uncorrected for an extended period. In a recent RCT, we found that 
61% of 477 women with OL were acidotic (lactate >4.8 mmol/L), with a median capillary blood lactate level 
of 6.9 (3.4–13) mmol/L.  In Mbale hospital, perinatal mortality rate is twice the national average of 48 per 
1,000 total births [6]. In the Sodium Bicarbonate in Obstructed Labour (SoBicOL) trial, 34% of the newborns 
had an Apgar score of less than seven, and 12% resulted in early neonatal deaths despite being 
resuscitated [7]. At two years of age, two thirds of the children born in this cohort had a 
neurodevelopmental delay [8]. These adverse outcomes may be averted by correcting the metabolic 
acidosis in obstructed. 
Currently, preoperative intravenous fluid infusion (1.5L of normal saline) is a component of the standard 
preoperative care for all women with OL [9]. Although this practice is adequate to correct electrolyte 
imbalances and dehydration in most women, it may not be sufficient to reverse the metabolic acidosis. In 
the SoBicOL trial [7], a single dose of 4.2g was insufficient to achieve significant changes in maternal or 
neonatal lactate levels in comparison to a placebo.  We postulate that our choice of a single dose regimen 
was too conservative, and only one measurement for the primary outcome at one hour was not ideal. The 
effect of sodium bicarbonate on maternal blood lactate was only noticeable more than one hour after the 
intervention. Currently, it is not known if a higher dose of bicarbonate would reverse the acidosis and 
achieve clinical benefits for the mother and baby.  
Therefore, we propose to undertake a placebo-controlled, dose-ranging pilot trial to determine the efficacy 
and safety of a preoperative infusion of sodium bicarbonate on acidosis, compared with placebo among 
women with obstructed labour (OL). We believe this is important because very often, 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 a low resource setting.  
Our results will inform the design of a full-scale effectiveness phase III trial to determine the effect of this 
preoperative infusion on maternal and perinatal outcomes. 
We hypothesize that a higher dose of bicarbonate, can safely lower the pH and lactate levels (metabolic 
acidosis) by at least 20%. Therefore, we aim to determine the effect and safety of a preoperative infusion 
of sodium bicarbonate on pH and lactate levels (metabolic acidosis) among women with obstructed labour. 
Problem statement 
In Uganda, obstructed labour (OL) directly accounts for 8% of all maternal deaths and up to 14.2% of the 
perinatal mortality rate [7]. In a recent RCT at Mbale hospital, we found that 61% of 477 women with OL 
were acidotic (lactate >4.8 mmol/L), with a median capillary blood lactate level of 6.9 (3.4–13) mmol/L [7]. 
In the same RCT, 34% of the newborns had an Apgar score of less than seven (7), and 12% resulted in early 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 5 of 25 
neonatal deaths despite being resuscitated. 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 acidosis 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. 
Therefore, we propose to undertake a placebo-controlled, dose-ranging pilot trial to determine the efficacy 
and safety of a preoperative infusion of sodium bicarbonate on acidosis, compared with placebo among 
women with obstructed labour (OL). 
Justification 
Undertaking a placebo-controlled, dose-ranging pilot trial shall establish a universal safe and effective dose 
of sodium bicarbonate for use to correct the acidosis among women with obstructed labour. Our results 
will inform the design of a full-scale effectiveness phase III trial to determine the effect of this preoperative 
infusion on maternal and perinatal outcomes. Furthermore, this information will facilitate the inclusion of 
sodium bicarbonate infusion in the standard preoperative preparation for women with obstructed labour 
in a low resource setting. 
Objectives 
General objective 
To determine the efficacy and safety of a preoperative infusion of sodium bicarbonate on pH and lactate 
levels (metabolic acidosis) among women with obstructed labour. 
Specific objectives 
 
1. To determine the efficacy of a preoperative infusion of sodium bicarbonate on acidosis, compared 
with placebo among women with obstructed labour (OL). 
2. To determine the safety of a preoperative infusion of sodium bicarbonate compared with placebo 
among women with obstructed labour (OL). 
Hypothesis 
We hypothesize that a higher dose of bicarbonate can safely lower the lactate levels (metabolic acidosis) 
by at least 20%.  
 
 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 6 of 25 
Methods and materials 
Study design 
We will conduct a dose-finding phase III, randomized, double-blind, placebo-controlled, parallel-group trial. 
Study setting  
Mbale regional referral and teaching hospital is a busy center in Eastern Uganda with a catchment 
population of over 4-5 million people. Based on the annual hospital medical records, over 10,000 births 
occur annually with a caesarean section rate of 35%; about 12% of these operations are due to obstructed 
labour.  
Study population 
Eligibility criteria: 
 
 
 
 
 
 
 
 
 
Study procedures 
A research team member will inform all patients and their attendants while in the waiting/admission area 
about the ongoing study as part of the routine health education talks in the unit. Mothers that express no 
further interest in participating in the study will be noted and not approached again about the same. 
On the other hand, those that express interest in knowing more about the study will be approached by a 
study team member once a diagnosis of obstructed labour is confirmed by the attending physician. The 
mother will be given more information about the study and a verbal consent will be obtained using a pre-
written script in their local language following the short verbal consent in Appendix 2. She will also be 
informed that the research midwife will approach her after the birth to seek formal consent to the use of 
the data and specimens collected during labour. 
After getting consent from the mother, the research midwife will take the next sequentially labelled study 
drug package and administer its contents to the consented eligible participant. At baseline, five milliliters 
of maternal venous blood will be collected: 2 mls in an Ethylenediaminetetraacetic acid (EDTA) vacutainer 
for a full blood count, and 3 mls in a general vacutainer (red top) for electrolytes, renal function tests, liver 
function tests and for grouping and cross matching. Ten milliliters of fresh urine will also be collected in a 
sterile container for analysis. All the specimens will be analysed using the RAPID Point® 500e Blood Gas 
System which is stationed in the surgical HDU, a short distance away from the labour ward. Lactate in 
amniotic fluid will be measured at the bedside using a hand-held Lactate Pro2 device (Arkray Factory, 
Inclusion Criteria:  
We will include patients 
with OL carrying singleton, 
term pregnancies (≥37 
weeks of gestation) in 
cephalic presentation. 
Exclusion Criteria:  
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. 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 7 of 25 
Japan). After administration of the study drug, all the participants will be actively monitored by a research 
midwife up to 24 hours in order to identify any adverse effects.  The research midwife will also use an 
electronic interviewer administered questionnaire to collect sociodemographic and clinical information 
from the participant at recruitment and during their stay in the hospital up to 14 days postpartum. Details 
of the study procedures are in the study flow diagram, figure 1. 
 
Figure 1: Study flow diagram for the proposed procedures 
Sample size estimation and sampling 
We will recruit 280 participants; 70 in each of the four arms. Wiberg-Itzel et al [2] observed mean umbilical 
artery pH 7.23 (SD 0.07) in the non-intervention group. With our sample size, we will have 80% power 
(significance level 0.05) to detect mean pH changes of 0.04 and above in each arm. We are interested in 
detecting an effect size of 0.2 and above, which we deem to be a moderate effect size. The total sample 
size needed to detect a between-factor mean effect size of 0.2, by repeated measures analysis of variance 
(ANOVA) with a type 1 error margin of 5%, across 4 groups with 5 repeated measurements; was 224 at a 
power of 91%. Assuming a 20% loss to follow up in our study; we will need 280 participants (70 in each of 
the 4 groups). The sample size was calculated using G* Power software version 3.1 using the test family for 
the F test, and the statistical test for ANOVA repeated measures, between factor analysis & within-
between interaction [10]. Therefore, our sample size will also be sufficient to detect a within and between-
subject interaction (intervention and time interaction) with a power of 99%. To obtain these estimates, we 
will construct an interaction term between the intervention and the time variable. We are confident that 
we shall be able to accrue this number of participants in a period of six calendar months, on the basis of 
our experience working in the same hospital [7]. In order to detect a change in maternal pH, a minimum of 
two measurements are needed from a participant. However, with improvement of obstetric care, many 
women deliver within 30 minutes of taking the baseline measurements and hence no second 
measurement is obtained. To account for this form of right censoring, we have inflated our sample size by 
192 participants to ensure that we have at least 280 women with at least two pH measurements. We will 
recruit 472 participants; 118 in each of the four arms.  
Outcome variables 
The primary outcome measure will be the mean change in maternal pH from baseline in each group. The 
secondary outcomes will include, mean pH and lactate in maternal and umbilical blood, early neonatal 
death, safety (side effects) of sodium bicarbonate, primary PPH, sepsis and death. Furthermore, the plasma 
concentrations of HCO3 levels will be measured as well to accurately estimate the required dose. 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 8 of 25 
Secondary outcomes will include neonatal death, postpartum haemorrhage and sepsis, in addition to the 
pharmacokinetics of sodium bicarbonate infusion in pregnant women. Details of measurements are in 
table 1. 
The independent variables will include the sociodemographic, clinical, and obstetric characteristics of the 
study participants at different time points as indicated in table 1.  
Table 1: Measurements to be taken from the participant samples 
Activity/ procedure 
Time in minutes 
Comment  
Baseline 
(0) 
30 60 90 120 150 At 
birth  
Metabolites (lactate & 
glucose) 
X 
X 
X 
X 
X 
X 
 
Bedside using the RAPID Point 
500e or YSTE-BG100 Blood gas 
analyzer 
Blood gases (pH, pCO2, 
pO2) 
X 
X 
X 
X 
X 
X 
X 
Serum Electrolytes 
(Na+, K+, Ca2+, Cl-) 
X 
X 
X 
X 
X 
X 
X 
Umbilical cord blood 
for lactate 
 
 
 
 
 
 
X 
Bedside using the RAPID Point 
500e or YSTE-BG100 Blood gas 
analyzer 
Myometrial Lactate 
only collected at 
Caesarean section 
 
 
 
 
 
 
X 
Bedside using the RAPID Point 
500e or YSTE-BG100 Blood gas 
analyzer 
Creatinine  
X 
 
 
 
 
 
 
Total of 5 mL of venous blood will 
be taken to a central laboratory; 
these are part of the standard 
care for each patient. 
Liver function tests 
(ALT&AST) 
X 
 
 
 
 
 
 
Full blood count 
X 
 
 
 
 
 
 
Amniotic fluid lactate* 
X 
 
 
 
 
 
 
Lactate Pro device 
Bicarbonate 
concentrations in 
plasma 
X 
X 
X 
X 
X 
X 
X 
Bedside using the RAPID Point 
500e or YSTE-BG100 Blood gas 
analyzer 
 
 
 
 
 
 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 9 of 25 
 
 
 
 
 
 
Figure 2: Flow of participants in the trial from screening to analysis 
 
Recruitment and data collection from participants 
Participants: Obstructed labour will be diagnosed by either an obstetrician or medical officer using a 
definition of the American Association of Obstetricians and Gynaecologists (ACOG).  In the first stage of 
labour, the participant should have cervical dilatation >6 cm with ruptured membranes, adequate 
contractions lasting >4 hours with no change in cervical dilatation or delay in the second active stage of 
labour (nullipara >2 hours, multipara >1 hour) with adequate uterine contractions. In addition, any two of: 
the obvious signs of severe obstruction such as caput formation, severe moulding, Bandl’s ring, 
subconjunctival haemorrhages or an oedematous vulva. 
Randomisation: A sequence of random numbers will be generated by an independent biostatician using an 
online randomization service at www.sealedenvelope.com in permuted block sizes of four, six and eight.  
An independent, off-site pharmacist will prepare and consecutively number identical study packages using 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 10 of 25 
the generated random numbers. This will ensure that the allocation is concealed. At the study site, after 
gaining consent, the research midwife will take the next sequentially labeled study drug package and 
administer its contents to the eligible participant. Therefore, both the participants and data collectors will 
remain blinded throughout the study. 
Intervention/ Comparator: Eligible participants will be randomly assigned to receive 100 mls (8.4g), 150 
mls (12.6g) and 200 mls (16.8g) of 8.4% sodium bicarbonate solution, or placebo (50 mls of NS 0.9%) in a 
ratio of1:1:1:1. The study drug (Sodium Bicarbonate 8.4% and Normal Saline 0.9%) will be contained in 
identical 25 mL glass vials (Neon Laboratories Ltd, Mumbai, India), administered intravenously as a single 
bolus dose. Since the average waiting time for CS in our labour ward is approximately 110 minutes [11], 
there will be no need for a repeat dose. 
In addition, all patients will receive the available Ministry of Health recommended standard preoperative 
care for all patients with OL which includes antibiotic prophylaxis, intravenous fluid replacement (1.5 L of 
normal saline), bladder drainage and lying in left-lateral position as they are being prepared for caesarean 
section [23]. Details in flow diagram 1. 
Data collection 
Our research assistants will be qualified midwives with training in data collection, using dedicated 
password protected android devices. We will also review relevant health facility records such as antenatal 
care cards, case notes/file, the maternity and theatre registers. Laboratory parameters including lactate 
will be measured at baseline, and every thirty minutes after study drug administration until delivery to 
obtain samples for lactate measurement in umbilical cord blood and the myometrium. The participants will 
be followed for 7 days postnatal to ascertain the secondary perinatal outcomes and for 14 days 
postpartum to determine the secondary maternal outcomes. In the first 24 hours after study drug 
administration, the participants will be closely monitored to identify any drug reactions/adverse events.  
After administration of the study drug, all the participants will be actively monitored by a research midwife 
up to 24 hours. The women will be examined and asked directly about the presence of side effects. 
Sample collection quality control 
Qualified and well-trained research midwives will draw five millilitres (ml) of blood by venipuncture at the 
antecubital fossa of the non- dominant arm from each participant using a five millilitres syringe. After 
removing the epidermal needle and the tops of the vacutainers, two millilitres will be emptied into a 
purple top vacutainer for a full blood count, blood grouping and cross-matching as part of the standard 
preoperative preparation for all patients with obstructed labour in the hospital. The remaining three 
millilitres will be emptied into a red top vacutainer for blood chemistries including electrolytes, these are 
not part of the routine preoperative preparation for patients before caesarean section. Each blood sample 
will be transported to the laboratory in an ice-cooled container within 30 minutes of collection. Urine 
samples: Mid-stream urine, ten millimeters will be collected in sterile urine container from the mothers. 
We will monitor strict adherence to the standard operating procedures for collecting and handling 
participant samples through ongoing training and spot checks.  
Cord blood collection 
After the baby is born, the midwife will double clamp and cut the umbilical cord. Cleanse a 4”- 6” area of 
the umbilical cord with alcohol to remove maternal blood and contaminants (before the delivery of the 
placenta, if possible). Then blood will be drawn from the cord with a needle. 
Data analysis plan 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 11 of 25 
Data will be analyzed using Stata version 17.0 (StataCorp; College Station, TX, USA). We will describe 
categorical variables as proportions and compare them with chi-squared tests or Fischer’s exact tests as 
appropriate. We will describe continuous variables as means (SD) OR medians (IQR) and compare them 
with t tests or Mann-Whitney U tests as appropriate. Our analysis will be by intention to treat. To 
determine the safety of sodium bicarbonate infusion, we will compare the incidence of side effects in each 
arm and report risk differences.  
For the primary outcome of acidosis (pH and lactate) between-subjects repeated measures ANOVA will be 
conducted. We will also conduct within-subject interaction repeated measures ANOVA to assess for 
differences in the rate of change of pH between the groups. 
We will use histograms, P-P plots, k-density, and Q-Q to assess the distribution of normality of continuous 
outcomes. In case the distribution of normality is not met; we shall transform our data and this decision 
will be guided by Stata’s gladder command that shows various transformation options. 
All analyses will be followed by a Bonferroni posthoc test for multiple comparisons, a Friedman test to 
compare rates of change between the various groups, and a Mauchly's test of Sphericity to check for equal 
variance among the combinations of the various groups. We will use Margins and Margins plots to obtain 
marginal means and graphical descriptions of the interaction between various groups and time. 
Data Monitoring 
Independent Data Monitoring Committee (IDMC) 
An independent data monitoring committee (IDMC) will be appointed consisting of 3 members: a 
statistician, an obstetrician/gynaecologist, and a paediatrician. They will operate according to the IDMC 
charter, which will be developed with the members. IDMC will be encouraged to follow the 
recommendations of the international DAMOCLES group for IDMC activities.[12] The IDMC will monitor the 
trial once with a focus on issues relating to the quality of trial conduct, such as overall and site-specific 
rates of recruitment, adherence to trial interventions, visit schedules, losses to follow-up, and 
administrative and safety data. It will review administrative and safety data approximately every three 
months. The treatment groups will be masked in the IDMC reports. 
Interim analyses and stopping guidelines 
Interim analyses: The interim analysis of efficacy data will be performed by the IDMC statistician. One 
analysis will be conducted according to the group sequential design when 50% of the inclusions are 
recorded. According to the O'Brien-Fleming alpha spending function, using a group sequential design and 
assuming a power of 80% and a significance level of 5%, the first interim analysis includes 140 subjects and 
has an information rate of 50%, efficacy bounds of -2.96 and 2.96, and p-value 0.003 (figure 3). These 
calculations were made using the RPACT RShiny app (https://rpact.shinyapps.io/public/). Interim trial data 
will be kept confidential and restricted to the IDMC, except if early stopping of the trial is recommended.  
 
 
 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 12 of 25 
 
Figure 3: Figure showing efficacy bounds (critical value) at the interim analyses (50% accrual rate) and how 
these will change as the study progresses 
Stopping guidelines 
1. We propose the following stopping rule: “a statistically significant difference (p<=0.003) at the 
interim analysis according to the O'Brien-Fleming spending function for group sequential design) in 
the primary outcome between the treatment arms. 
2. SAEs will be continuously monitored during data entry and reported to the IDMC. Any imbalance 
between expected occurrence and actual occurrence will be assessed by the IDMC statistician when 
50% inclusions are recorded, and discussed with the IDMC. 
3. The IDMC will provide a recommendation to stop or alter the design or conduct of the trial in case 
of high efficacy and/or poor adherence or unacceptable side effects that can be ascribed to the 
intervention according to pre-determined stopping rules and criteria. While the reviews of safety 
will consider both expected or unexpected adverse events, and the relative rates of death.  
4. If the IDMC recommends stopping the trial early, a meeting of the principal investigator, the trial 
sponsor, the trial steering committee and the IDMC will be held to decide on the trial 
discontinuation. In case of disagreement, the advice of independent external experts will be sought. 
A report will be submitted to the Local IRB (BUIRB) as soon as possible and not later than 14 days 
after the decision. 
 Ethics and consent process 
Ethical approval will be sought from the Busitema University Research and Ethics Committee (REC), and the 
Uganda National Council for Science and Technology (UNCST). We shall also seek ethical clearance from 
the University of Bergen in Norway, since it is a requirement for our collaborators. Administrative 
clearance to conduct the study will be obtained from the Mbale Hospital Research and Ethics Committee. 
The Ministry of Health and hospital protocols will be followed in management of emergencies such as 
neonatal resuscitation during the study [13].  
Informed consent will be obtained in two steps as suggested in the differed consent pathway for 
intrapartum research [14]. In step one, a research team member will inform all patients and their 
attendants while in the waiting/admission area about the ongoing study. This will be done by the staff on 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 13 of 25 
duty as part of the routine general health education talks before a diagnosis of active labour or even 
obstruction is made by the attending physician.  Those who will express interest in knowing more about 
the study will be taken through the process of obtaining a short verbal consent if they become eligible 
(Appendix 3). We will keep an inventory of those that decline to participate at this stage, they will not be 
approached again and no data will be obtained regarding their births or outcomes. Once eligible, women 
will be informed about the study and verbal consent obtained using a pre-written script in their local 
language. Those who accept to be in the study will be administered the medication, whilst those who 
decline or are in any way unsure will not be included. In step two, after delivery in the postpartum period, 
the participant will be visited by a member of the research staff for the formal informed consent process. 
From past experience in this same labour ward this might be the scenario for most of the participants. In 
the case of illiterate participants, an independent witness will also be asked to witness the consent process 
and sign the consent form besides the participant’s thumb print. Pregnant women between 16 - 18 years 
of age will be included as emancipated minors, who can give a valid informed consent as per the national 
guidelines [15].  
Budget 
Budget in USD 
Unit 
price 
No of 
units 
Freque
ncy 
Total  
Justification 
Personnel 
  
Research Assistants 
500 
4 
12 
24,000 
To offer 24-hour coverage, in the 
recruitment phase 
Project Initiation costs 
  
REC approval 
800 
1 
1 
800 
Both local and national, including a 
onetime annual renewal 
NDA clearance 
4000 
1 
1 
4,000 
Mandatory Fee, for all drug trials. 
Clinical trial insurance 
5000 
1 
1 
5,000 
One-time mandatory cost required 
by the National drug authority 
IDMC 
920 
1 
1 
920 
To facilitate one physical meeting, 
at the half way mark of data 
collection 
Site Initiation trainings 
500 
1 
1 
500 
One physical training every six 
months, one at initiation and one 
refresher 
Patients’ costs 
  
Participants compensation 
8 
290 
1 
2,320 
This is mandatory by REC to 
compensate for participants time 
in study 
Sundries and supplies- CS 
kit 
14 
100 
1 
1,400 
To try and reduce delays to access 
emergency CS due to lack of 
sundries. Assuming CS rate will 
remain 35% 
Treatment/Placebo costs 
  
Sodium bicarbonate 
infusion 
4 
2000 
1 
8,000 
Purchase of the active drug 
0.9% Normal Saline 
3 
100 
1 
300 
Purchase of the placebo 
Non-treatment consumables 
  
Lactate Pro 2 Device 
340 
1 
1 
340 
One additional device to 
supplement the two we have from 
the previous project 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 14 of 25 
Lactate Pro 2 test strips 
2 
290 
4 
2,320 
Every patient will need a minimum 
of four tests through labour 
Cartridges  
16 
290 
1 
4,640 
To be purchased from the local 
supplier for the RAPID Point® 500e 
Blood Gas System (Bedside 
Testing) 
Laboratory test 
12 
290 
1 
3,480 
Full blood count blood grouping 
and cross matching at baseline. 
Plasma concentrations of 
bicarbonate(pK) 
Antiseptic 
1 
290 
2 
580 
For collection of samples, at 
phlebotomy. 
Community engagement 
  
Community engagement 
involvement 
700 
1 
2 
1,400 
To facilitate the conduct of 
community engagement meetings 
Total 
` 
  
  
60,000 
This excludes 15% institutional 
overheads. 
 
Management  
The Principal Investigator (Dr. Milton Musaba) is an Obstetrician and Gynaecologist, who has just 
completed a trial on the use of sodium bicarbonate in obstructed labour in the same maternity unit, as part 
of his PhD training[7]. Dr. David Mukunya, is trial manager for BabyGel. He has managed several large trials 
and recently completed his PhD in Newborn morbidity and mortality under the Survival Pluss project in 
Northern Uganda. Prof Julius Wandabwa is an Obstetrician and Gynaecologist/Dean of the Busitema 
University Faculty of Health Sciences that will administer this grant as a lead institution. Dr. John Mulangwa 
will be providing support as a study pharmacist, he will import and blind the study drugs in liaison with the 
statistician. 
Independent Data Monitoring Committee  
We plan to conduct one interim analysis, when half (25%) of the participants have been recruited. This will 
be undertaken by the independent data monitoring committee (IDMC) composed of an obstetrician, a 
paediatrician and a statistician with research experience. These will be appointed by the sponsor of the 
study, Busitema University. The stopping rules agreed upon in the terms of reference for the IDMC will be 
based on: safety concerns, outstanding benefit, and futility. The IMDC will have the mandate to halt the 
study if the occurrence of adverse events (Safety) in any of the intervention arms is greater or equal to 10% 
in comparison to the placebo arm. All the serious adverse events (SAE’s) will be reported and closely 
followed, until resolution following the existing statutory guidelines. However, this is unlikely to happen 
because the active drug (sodium bicarbonate) has a very good safety profile in both clinical use and 
research even among pregnant women in children. Furthermore, we will ensure that our study protocol is 
approved by both the Busitema University Faculty of Health Sciences Research and Ethics committee 
(BUFHS), and the Uganda National Council for Science and Technology (UNCST).  
Quality control: All our research assistants will be qualified midwives/nurses, with training in good clinical 
practice (GCP). They will also receive training in the study protocol procedures during the trial dry run 
phase and at regular intervals throughout the implementation of the trial. The electronic questionnaire will 
be coded with checks and skips to ensure internal consistency.  All the required blood tests will be done at 
the bedside using the RAPIDPoint® 500e Blood Gas System (Siemens Healthcare GmbH)[16]. Our choice of 
this system was informed by its ability to measure a range of parameters, using only 100 microliters of 
blood. Additionally, women with obstructed labour requiring urgent intervention, hence the need for a 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 15 of 25 
short turnaround time on blood results to inform clinical decision making. In the event of system 
downtime, we will use a YSTE-BG100 Blood Gas Analyzer (Yuesen Med, China) as a backup. The YSTE-
BG100 is a compact and user-friendly device that can rapidly assess key parameters including pH, lactate, 
glucose, electrolytes, and blood gases [17], thereby ensuring continuity of care even when the RAPIDPoint® 
500e Blood Gas System is down. In our previous trial the study drug was sourced from the local supplier 
accredited by the National Drug Authority (NDA). We intend to use 8.4% sodium bicarbonate 
(intervention), and sodium chloride 0.9% (placebo) from NEON laboratories Ltd, Mumbai, India. 
Adverse events/side effects: Based on the package insert labelling for sodium bicarbonate and a review of 
the literature [18], we will actively monitor for the following; increased thirst, continuing loss of appetite, 
swelling of the lower limbs, venous irritation, muscle pain or twitching, continuing headache, nausea or 
vomiting, stomach crumps, unusual tiredness or weakness, nervousness or restlessness, mood or mental 
changes, frequent urge to urinate, slow breathing and cellulitis at the injection site. This will be done 
hourly for the first six hours, six hourly for the next 18 hours and then daily throughout the period of 
hospitalization. 
Follow-on plan 
We plan to publish our results in a peer reviewed journal irrespective of the findings, as we have 
demonstrated in the past. Furthermore, we have established contact with Dr. Trond Michelsen in Oslo to 
advise on the setup of our current study. His group is undertaking similar work (https://ichgcp.net/clinical-
trials-registry/NCT05719467 ), and they could be potential collaborators on a larger grant application if the 
results are positive (see attached support letter). We have a community advisory group that is crucial in 
disseminating our findings to the lay public. Dr Musaba is also a member of National Safe Motherhood 
Executive Committee (NASMEC), a ministry of health technical advisory group on maternal health. He will 
disseminate the findings in this group. 
Table 2: Proposed study timelines 
Activity  
2024 
2025 
 
Ja
n  
Fe
b 
Ma
r 
Apri
l 
Ma
y 
Jun
e 
Jul
y 
Au
g 
Sep
t 
Oc
t  
No
v 
De
c  
Ja
n  
Fe
b  
Ma
r  
Ap
r  
Ma
y  
Jun
e  
REC & 
UNCST 
approvals 
* 
* 
* 
* 
* 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recruitment 
of staff 
 
 
 
 
* 
* 
* 
 
 
 
 
 
 
 
 
 
 
 
Procuremen
ts  
 
* 
* 
* 
* 
* 
* 
* 
* 
* 
* 
 
 
 
 
 
 
 
Data 
collection 
 
 
 
 
 
 
* 
* 
* 
* 
* 
* 
* 
* 
* 
* 
* 
* 
Data 
analysis  
 
 
 
 
 
 
 
 
 
 
* 
* 
* 
* 
* 
* 
* 
* 
Disseminati
on and 
Publications 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* 
* 
* 
* 
 
 
 
 
 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 16 of 25 
 
 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 17 of 25 
Pharmacokinetics of sodium bicarbonate   
Study design:    This will be a population-based pharmacokinetics study of sodium bicarbonate using 
plasma levels in pregnant women with obstructed labour. We propose to investigate the association 
between the exposure of various doses of sodium bicarbonate (i.e. 8.4g, 12.6g and 16.8g) in pregnant 
women with obstructed labour, and identify determinants to inform dosing policy guidelines. 
Study population: We will establish a cohort of pregnant women with obstructed labour in Mbale regional 
referral hospital. Only mothers that consent to participate in the study will be included. 
Data collection: Following the administration of sodium bicarbonate, a blood sample will be collected from 
the mother at time 30, 60, 90, 120 and 150 minutes and at the time of childbirth; and then umbilical cord 
blood will be collected at birth for testing. Consequently, the concentrations of sodium bicarbonate will be 
determined using liquid chromatography (HPLC) method with electrochemical detection as described by 
Rodriguez [19]. The HPLC analysis will be conducted at Busitema University Ministry of Science, Technology 
and Innovation supported laboratory. Data from the respective participants will include PK, socio-
demographics, adverse events and other clinical parameters including weight and age.  
Data analysis: Non-compartmental analysis will be used to analyse the intensive PK data for sodium 
bicarbonate and a population pharmacokinetic model will be developed to analyse the sparse PK data.  Any 
disparate treatment approached, additional medications or relevant clinical information, will be captured 
and adjusted for in the model. We will use nonlinear mixed-effects modelling (also known as population 
PK) to interpret the sodium bicarbonate pharmacokinetic data and assess the effect of variation. PopPK 
modelling offers a semi-mechanistic platform to interpret PK data, in that it evaluates the effect of patient 
covariates on physiological PK parameters (such as clearance and bioavailability), as opposed to 
hydroxyurea concentrations summary values (such as AUC and Cmax). The concentration-time data for the 
drugs of interest will be analysed using popPK (nonlinear mixed-effects) modelling in NONMEM. 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 18 of 25 
References 
1. 
Wray S: Insights into the uterus. Experimental Physiology 2007, 92(4):621-631. 
2. 
Wiberg-Itzel E, Pembe AB, Järnbert-Pettersson H, Norman M, Wihlbäck AC, Hoesli I, Todesco Bernasconi M, 
Azria E, Åkerud H, Darj E: Lactate in Amniotic Fluid: Predictor of Labor Outcome in Oxytocin-Augmented 
Primiparas' Deliveries. PLoS One 2016, 11(10):e0161546. 
3. 
Quenby S, Pierce SJ, Brigham S, Wray S: Dysfunctional labor and myometrial lactic acidosis. Obstetrics and 
gynecology 2004, 103(4):718-723. 
4. 
Aminu M, Bar-Zeev S, White S, Mathai M, van den Broek N: Understanding cause of stillbirth: a prospective 
observational multi-country study from sub-Saharan Africa. BMC Pregnancy and Childbirth 2019, 19(1):470. 
5. 
"Ministry of Health u: Annual Health sector performace report In.: Goverment of Uganda; 2019/20. 
6. 
Nankabirwa V, Tumwine JK, Tylleskär T, Nankunda J, Sommerfelt H: Perinatal mortality in eastern Uganda: a 
community based prospective cohort study. PLoS One 2011, 6(5):e19674. 
7. 
Musaba MW, Wandabwa JN, Ndeezi G, Weeks AD, Mukunya D, Waako P, Nankabirwa V, Mugabe KT-m, 
Semakula D, Tumwine JK: Effect of pre-operative bicarbonate infusion on maternal and perinatal outcomes 
among women with obstructed labour in Mbale hospital: A double blind randomized controlled trial. PloS 
one 2021, 16(2):e0245989. 
8. 
Musaba MW, Ndeezi G, Barageine JK, Weeks AD, Wandabwa JN, Mukunya D, Waako P, Odongkara B, Arach 
A, Tulya-Muhika Mugabe K: Incidence and determinants of perinatal mortality among women with 
obstructed labour in eastern Uganda: a prospective cohort study. Maternal health, neonatology and 
perinatology 2021, 7:1-9. 
9. 
WHO: WHO recommendations: intrapartum care for a positive childbirth experience. In.; 2018. 
10. 
Faul F, Erdfelder E, Lang A-G, Buchner A: G*Power 3: A flexible statistical power analysis program for the 
social, behavioral, and biomedical sciences. Behavior Research Methods 2007, 39(2):175-191. 
11. 
Apako T, Wani S, Oguttu F, Nambozo B, Nahurira D, Nantale R, Kamwesigye A, Wandabwa J, Obbo S, Mugabe 
K et al: Decision to delivery interval for emergency caesarean section in Eastern Uganda: A cross-sectional 
study. PLOS ONE 2023, 18(9):e0291953. 
12. 
Damocles Study Group: A proposed charter for clinical trial data monitoring committees: helping them to 
do their job well. The Lancet 2005, 365(9460):711-722. 
13. 
Health UMo: Uganda clinical guidelines 2016. 2016. 
14. 
Vernon G, Alfirevic Z, Weeks A: Issues of informed consent for intrapartum trials: a suggested consent 
pathway from the experience of the Release trial [ISRCTN13204258]. Trials 2006, 7(1):1-6. 
15. 
Science UNCo, Technology: Guidelines for the conduct of health research involving human subjects in 
Uganda. In.: UNCST Kampala, Uganda; 2007. 
16. 
Jeong TD, Kim SK: Performance of the New RAPIDPoint 500e Blood Gas Analyzer and its Comparison with 
Central Laboratory Biochemistry Analyzer. Clin Lab 2022, 68(9). 
17. 
YSENMED YSTE-BG100 Blood Gas Electrolyte Analyzer [https://www.ysenmed.com/products/blood-gas-
analyzer-catalog-yste-bg100] 
18. 
Senewiratne NL, Woodall A, Can AS: Sodium Bicarbonate. 2020. 
19. 
Rodriguez A, Beukens D, Debouge N, Gulbis B, Cotton F: Development and validation of a liquid 
chromatography method with electrochemical detection for hydroxyurea quantification in human plasma 
and aqueous solutions. J Chromatogr Sep Tech 2014, 5:244-247. 
20. 
Maitland K, Molyneux S, Boga M, Kiguli S, Lang T: Use of deferred consent for severely ill children in a multi-
centre phase III trial. Trials 2011, 12(1):90. 
 
 
 
 
 
 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 19 of 25 
 
 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 20 of 25 
Appendix 1: Data collection tool  
A. Sociodemographic details 
1. Study ID………. 
2. Today date …/…./…… 
3. Date of admission …/…./…… 
4. Time of admission …/…./……  
5. Contact details of participant …………………. 
6. Participants next of kin 
i. Partner  
ii. Sibling  
iii. In-law 
iv. Others  
7. What is the contact of the next of kin?...................... 
8. Age of the participant ………………….. 
9. What best describes your religion? 
i. Catholic  
ii. Anglican  
iii. Muslim  
iv. SDA 
v. Pentecostal  
vi. Others  
10. What best describes the participants marital status? 
i. Single  
ii. Married  
11. What best describes the participants completed level of education? 
i. No education 
ii. Primary  
iii. Secondary  
iv. Tertiary  
12. What best describes the participants occupation? 
i. Salaried employee 
ii. Self employed 
iii. Housewife  
13. How would the participant best describe her place of residence? 
i. Urban  
ii. Rural  
14. How far is the participants home from the nearest health facility 
i. < 5Km 
ii. > 5Km 
B. Obstetric history 
1. What is participants parity? 
i. 0 
ii. 1 to 2 
iii. 2 to 4 
iv. 5+ 
2. What is the estimated gestation age of the current pregnancy? 
3. Did the participant attend ANC for the current pregnancy? 
i. Yes  
ii. No  
4. If yes, how many times did you attend? 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 21 of 25 
5. Date of labour onset 
6. Time of labour onset 
7. Have your waters broken? 
i. Yes  
ii. No  
iii. Not sure 
8. If yes, when did the waters break? 
i. Date  
ii. Time  
9. Did the participant come in as a referral? 
i. Yes  
ii. No  
10. If yes, from which facility 
i. Hospital  
ii. HC II 
iii. HC III 
iv. HC IV 
v. Private  
vi. TBA 
11. Has the participant use any traditional medicines in the current pregnancy? 
i. Yes  
ii. No  
C. Clinical examination findings 
1. Weight  
2. Height  
3. BMI 
4. Cardiovascular system  
i. BP 
ii. Pulse  
iii. SPO2 
5. Respiratory system 
i. Respiratory rate 
6. Abdominal examination 
i. Does the participant have a visible Bandl’s ring? 
ii. Doe the participant have palpable uterine contractions? 
iii. What is fetal heart rate? 
7. Vaginal examination  
i. Is the vulva and vagina oedematous? 
ii. Is the caput present? 
iii. Is the pelvis adequate? 
iv. Have the membranes ruptured? 
v. What is the colour of the liquor? 
D. Baseline laboratory test results - Maternal 
 
Parameter  
Blood  
Amniotic fluid  
Urine  
pH 
 
Not Applicable 
Not applicable 
Blood gasses 
 
Not Applicable 
Not applicable 
Lactate 
 
 
 
 
E. Study drug administration 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 22 of 25 
 
Time  
 
Package number  
 
 
F. Maternal outcomes after study drug administration 
 
Time (minutes) 
Lactate in 
maternal blood 
sample 
Lactate in 
amniotic fluid 
sample 
Maternal 
arterial blood 
gasses  
Maternal pH 
0  
 
 
 
 
30 
 
 
 
 
60 
 
 
 
 
90 
 
 
 
 
120 
 
 
 
 
150 
 
 
 
 
 
G. Maternal outcomes at birth 
1. Mode of delivery  
i. SVD 
ii. CS 
2. For all those that delivered by CS, record the myometrial lactate here 
3. What was the duration of labour? 
4. Measured blood loss at birth 
5. How well did the uterus contract after birth? (scale 1-10) 
6. Assistant at delivery? 
i. Midwife 
ii. Specialist  
iii. Medical Officer  
iv. Intern  
v. Student  
vi. Others 
7. Did the participant sustain any injuries in the birth canal? 
i. Yes  
ii. No  
H. Newborn outcomes at birth 
1. Record the Agar score here 
i. At one minute 
ii. At five minutes 
2. Record the birth weight here 
3. Lactate in arterial cord blood 
4. Lactate in venous cord blood 
Within one minute 
of child birth 
Lactate in 
maternal blood 
sample 
Lactate in 
amniotic fluid 
sample 
Maternal 
arterial blood 
gasses  
Maternal pH 
Arterial cord blood 
 
 
 
 
Venous cord blood 
 
 
 
 
 
I. Monitoring of side effects and adverse events for 24 hours period after administration of study 
drug 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 23 of 25 
(Tick all that apply) 
 
1.  Frequent urge to urinate 
10. Swelling of feet or lower legs 
2. Headache (continuing) 
11. Unpleasant taste 
3.  Loss of appetite (continuing) 
      12.  Increased thirst 
4.  Mood or mental changes 
    13. Unusual tiredness or weakness 
5.  Muscle pain or twitching 
14. Venous irritation 
6.  Nausea or vomiting 
   15. Cellulitis 
7.   Stomach crumps 
   16. IV site pain 
8.   Nervousness or restlessness 
9.    Slow breathing 
 
J. Follow up outcomes 
1. Perinatal outcomes on the 7th day postnatal 
i. Alive and well  
ii. Alive and not well  
iii. Dead  
2. If baby is alive and not well or Dead, please specify why; 
3. Maternal outcomes on 4th day postpartum 
i. Alive and well 
ii. Alive and not well 
iii. Dead  
4. If mother is alive and not well or Dead, please specify why;  
 
K. Pharmacokinetic of hydroxy urea in pregnant women 
Time (minutes) 
Maternal blood 
Urine  
Amniotic fluid   
Umbilical 
blood  
0  
 
 
 
 
30 
 
 
 
 
60 
 
 
 
 
90 
 
 
 
 
120 
 
 
 
 
150 
 
 
 
 
 
 
 
 
 
 
 
 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 24 of 25 
Appendix 2: Short Verbal Consent form [20] 
i. 
When the process of your labour does not happen as expected, it is called obstructed 
labour. This may need you to have a caesarean section for a safe delivery.  
ii. 
Most women in your situation have built up a lot of acid in their blood and this can be 
harmful for both you and your baby. An infusion called sodium bicarbonate can reduce this 
acidity, improving outcomes for you and your baby. However, we do not know how much of 
the drug, women need, nor whether mothers and babies do better if they receive it. 
iii. 
If you want to take part in this research, we will use a computer to decide what dose of the 
drug we will give you – or whether we just give you plain water. Neither you nor the doctor 
will know what dose you have received but we will monitor you carefully and take off some 
samples at different time points. We will use that information to improve the care for 
women in the future who have the same condition as you. 
iv. 
We have independent committees reviewing the study to make sure that the study is safe 
for you and your baby. However, if you do not want to take part in research you can simply 
refuse and we will give you the usual treatment instead.  
Would you like to take part in this research? 
Name of Participant                                              Signature/Thumbprint                                        Date 
………………………………… …………………………….          ………………………                  …………………………….. 
Name of person obtaining consent                         Signature                                    Date 
………………………………… …………………………….          ………………………                  …………………………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 25 of 25 
Appendix 3: English Consent form 
Title of the study: 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) 
Principal investigator: Dr. Milton Musaba, Associate Professor of Obstetrics and Gynecology, Busitema 
University. 
Background of the study 
When a woman is in labor, sometimes the baby can get stuck possibly due to the baby being big or the 
birth canal being small, making it difficult for the baby to come out. This is called obstructed labor. When 
this happens, the muscles that make up the womb work really hard and for a long time, this extra effort 
reduces the oxygen that eventually reaches the unborn baby through the muscles of the womb. As a result, 
a substance called lactic acid can build up in the mother's blood and around the unborn baby. If the 
arrested labour process is not relieved quickly, the acid accumulates in the mother’s womb and blood 
stream, the excess acid can also easily reach the unborn baby through the umbilical cord leading to 
unwanted consequences for the mother and baby pair including death.  
We believe that giving a solution called sodium bicarbonate (SODA ASH) to women with arrested labour as 
they wait to get a caesarean section, can help to reduce this excess acid and improve outcomes for both 
the mother and unborn baby. Based on results from our previous work and that of other colleagues in the 
world, this drug is very safe for pregnant women and their unborn babies. However, what remains 
unknown to date is what the most effective and safe dose should be?    
Study purpose 
The purpose of this study is to identify the safest effective dose that can be used to reduce acidosis in 
women with arrested labour in Mbale hospital. Knowing what the right dose should be, will inform the 
design of a larger study to determine the usefulness of this treatment to improve maternal and fetal 
outcomes among women with obstructed labour in our region and beyond. 
Who is requested to participate? 
Mothers with obstructed labour admitted at the labour ward of Mbale regional referral hospital 
Study procedures 
If you choose to participate in this study, we will collect five milliliters (5mls) of blood from you; 2 mls in a 
purple top container for a full blood count, and 2 mls in a red top container for electrolytes, renal function 
tests, liver function tests and grouping and cross matching and one ml will be taken in six equally divided 
portions for measuring lactate in your blood, glucose, and blood gases (pH, pCO2, pO2) at different time 
points. We will also collect ten milliliters (10 mls) of fresh urine in a sterile container for analysis. Further, 
lactate in the fluid around the baby will be measured at the bedside using a hand-held Lactate Pro2 device. 
You will also be assigned by chance to one of four treatment groups to receive different doses of the 
sodium bicarbonate (SODA ASH) drug. Additionally, one treatment group will receive only water for 
injection. Since, this allocation is purely based on chance, neither you nor any of the study team members 
can influence the choice of which group to belong to.  After administration of the study drug, you will be 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 26 of 25 
actively monitored by a research midwife up to 24 hours. You and your baby will be followed up till 14 days 
postpartum. 
Risks/discomforts: 
There may be minimal medical risks due to the drawing of blood samples such as mild, temporary 
discomfort at the venipuncture site, minor pain, bruising or bleeding. On rare occasions, there could be a 
risk for infection, fainting. However, these are not expected to happen since blood samples will be 
collected by qualified medical personnel. The volume of the blood sample to be collected is not likely to 
cause faintness and will not interfere with the normal process of pregnancy/labour. 
Benefits  
You will not receive and direct benefit from this study. However, information obtained from this study will 
improve maternal and fetal outcomes among women with obstructed labour in our region and beyond. In 
addition, a copy of all the results from the laboratory tests will be availed in your file for use by the 
attending clinicians to help in decision making regarding your care.  
Voluntary participation and right to withdraw consent:  
You are free to join the study or not to join. Your participation in this study is completely voluntary. If you 
would like to participate, please sign the consent form at the end of this document. If you join the study, 
you will be free to withdraw from it any time, and if you decline to participate in the study, you will still 
receive the same care and attention from the medical personnel(s). There will be no negative 
consequences for you or your baby if you do not want to participate or if you choose to withdraw at a later 
stage. If you withdraw your consent, your health data and biological material will not be used in any 
further research. You can request access to the data held on you, and this will be provided within 30 days. 
You can also apply for your data in the project to be deleted. 
The right to have your data and material destroyed, deleted or returned does not apply if the material or 
data are anonymized or have already been published. Access may also be restricted if the data have been 
included in analyses already performed. 
Confidentiality:  
Your names will not appear anywhere on the study forms. A study identification number will instead be 
used.  Only researchers involved in the study will be allowed to work with your blood and see your 
information. The information will only be used for the purpose of this study and no publication of this 
study will use your name or identify you personally. 
Reimbursement: 
Twenty thousand Ugandan shillings (UGX 20,000) will be given to you for your refreshment or time 
compensation. This is in accordance with guidelines of the Uganda National Council for Science and 
Technology (UNCST). 
Follow up project: 
In future, if funding is available, we may contact you for a follow up study. 

 
BUFHS-2024-164_Protocol_SoBicOL-II Study_V1.3_10 September 2025_Page 27 of 25 
Contact details: 
If you have any questions about your rights as a participant in this study, you can call the Busitema 
University Research and Ethics Chair chairperson, Dr. Richard Katuramu on 0752900344. If you have any 
other questions about the study, you can ask them now or later. If you wish to ask questions later, you may 
contact the Principal investigator: Prof. Milton Musaba, Associate Professor of Obstetrics and Gynecology, 
Busitema University.  P.O. Box 1460 Mbale, Uganda. Mobile: 0704913791. miltonmusaba@gmail.com  
STATEMENT OF CONSENT: 
I ……………………………………………………   confirm that the researcher has explained to me all the above 
information. I have understood what will be done, the risks, the benefits involved and my rights regarding 
this study. I understand that my decision to participate in this study will not alter my usual medical care. In 
the use of this information, my identity will be kept confidential. I am aware that I may withdraw at any 
time. I understand that by signing this form, I do not waive any of my legal rights but merely indicate that I 
have been informed about the research study in which I am voluntarily agreeing to participate. A copy of 
this form will be provided to me.  
Name of Participant                                          Signature/thumb print                                      Date 
………………………………… …………………………….          ………………………                 …………………………….. 
Name of Witness                                                                Date 
…………………………………………………………………….            ………………………………… 
Name of person obtaining consent                         Signature                                        Date 
………………………………… …………………………….          ………………………                      ……………………………..