Prevention of pre-eclampsia through vitamin D supplementation: a single-blinded randomized clinical trial without placebo

ISRCTN	ISRCTN46539495
DOI	https://doi.org/10.1186/ISRCTN46539495
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	Nil known
Sponsor	University of Lubumbashi
Funder	Investigator initiated and funded

Submission date: 11/11/2020
Registration date: 17/11/2020
Last edited: 09/02/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Pregnancy and Childbirth

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Pre-eclampsia is a condition that causes high blood pressure during pregnancy and after labour. It is the third highest cause of maternal death in the world. Vitamin D supplementation can counteract the changes in the placenta that cause the clinical symptoms of pre-eclampsia. The aim of this study is to evaluate the benefits of this supplement.

Who can participate?
Women who are pregnant for the first time

What does the study involve?
Participants are randomly allocated to one of two groups. The supplement group takes vitamin D by mouth as one dose per month from the 3rd to the 8th month of pregnancy. The control group will be followed in the antenatal clinic and will receive an iron supplement and anti-parasitic treatment. Blood samples will be collected at the start and the end of the study to measure vitamin D and calcium.

What are the possible benefits and risks of participating?
The participants may benefit from the reputed effects of vitamin D. The possible risks include side effects of vitamin D.

Where is the study run from?
University of Lubumbashi (Congo, Democratic Republic)

When is the study starting and how long is it expected to run for?
May 2017 to August 2021

Who is funding the study?
Investigator initiated and funded

Who is the main contact?
Dr Richard Kabuyanga Kabuseba
docrica@hotmail.com, richard.kabuseba@unigom.ac.cd

Contact information

Dr Richard Kabuyanga Kabuseba
Scientific

Camps Des Medecins Goma Nord-Kivu Rdc
Goma
243
Congo, Democratic Republic

Phone	+243 (0)99 44 99 001/+243 (0)813130100
Email	docrica@hotmail.com

Dr Richard Kabuyanga Kabuseba
Scientific

Camps Des Medecins Goma Nord-Kivu Rdc
Goma
243
Congo, Democratic Republic

Phone	+243 (0)99 44 99 001/+243 (0)813130100
Email	Richard.kabuseba@unigom.ac.cd

Study information

Primary study design	Interventional
Study design	Single-blinded randomized clinical trial without placebo
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Pre-eclampsia in Kivu: vitamin D levels and impacts of vitamin D supplementation on obstetric-neonatal outcomes in primigravida
Study objectives	Supplementation of pregnant women with vitamin D improves the health of primigravida (potentially at risk of preeclampsia) and the fetus safely.
Ethics approval(s)	Approved 08/02/2019, Ethics Committee of the University of Lubumbashi (B.P: 1825 Lubumbashi, Democratic Republic of Congo; +243 (0)995258703, +243 (0)997022438; clubabankulu2017@gmail.com, gabybora2003@yahoo.fr, Eth_med@yahoo.fr), ref: UNILU/CEM/125/2019
Health condition(s) or problem(s) studied	Pre-eclampsia
Intervention	Patients will be divided into two groups based on gestational age (randomized into two groups). Supplemented group: 60,000 IU of VITOSSAMIN® D3 (cholecalciferol) orally in one dose per month from the 3rd (≤15 weeks of amenorrhoea) to the 8th month of pregnancy, i.e. 360,000 IU in total. Control group: does not receive a placebo but will be followed in the ANC and will receive an iron supplement and anti-parasitic treatment. These are primigravidae recruited with a pregnancy age exceeding 15 weeks during the recruitment period and not having completed the second trimester. Blood will be collected at the recruitment stage and at the end of the trial to measure vitamin D and calcium. Laboratory monitoring will be performed twice at the 7th month and at the delivery. Selection and recruitment visit: During the 3rd month visit between 11 and 14 weeks supplemented pregnant women will be identified and their informed consent (written) obtained. Non-supplemented pregnant women are also selected during the ANC. Visits: The patients will be followed every month during the normal pregnancy follow-up (PNC) End of study visit: after the 34th week of pregnancy a blood sample will be collected for maternal and neonatal indicators.
Intervention type	Supplement
Primary outcome measure(s)	Percentage of patients with preeclampsia during pregnancy, evidenced by the occurrence of hypertension (systolic blood pressure [SBP] greater than or equal to 140 mmHg and/or diastolic blood pressure [DBP] greater than or equal to 90 mmHg, taken twice 4-6 hours apart, at rest) and 2 x proteinuria after 20 weeks of amenorrhoea
Key secondary outcome measure(s)	For the patients: 1. Gestational age for any incident and for preeclampsia, measured during antenatal care or other consultations by taking blood pressure, albuminuria measurement to confirm preeclampsia from recruitment (enrollment) to postpartum 2. Other clinical signs: given the atypical forms of preeclampsia, some clinical signs according to ACOG may allow the diagnosis of preeclampsia in the absence of proteinuria. The occurrence of these signs is monitored from the time of enrolment until delivery by means of an anamnesis, clinical and laboratory examination, and the pregnant woman is monitoring the antenatal care, of which she is aware 3. Incidents (eclampsia, detachment of the normally inserted placenta, maternal death) measured according to clinical, paraclinical (ultrasound and biology) examination from enrolment to postpartum (or death) 4. Serum concentration of 25OH-D, measured using iChroma II analyser (Boditech Med Inc, South Korea), at enrollment when the pregnant woman is carrying a pregnancy of age ≤14 weeks of amenorrhoea for the gestates to be supplemented and between 34 weeks of amenorrhoea and delivery (thus two samples for each subject), and for the other group after 14 weeks of amenorrhoea and between 34 weeks of amenorrhea and delivery In newborns: 1. Birth weight measured using scale at birth 2. Height measured using scale at birth 3. Cranial perimeter measured by tape measure by taking the circumference of the head through the glabella just after delivery 4. Intrauterine growth retardation noted at birth but detected by ultrasound as the pregnant woman is following ANC. Confirmation is done at birth with the use of tables 5. Death in utero observed after inclusion in the cohort (as it can occur at any time) and diagnosed by ultrasound before birth
Completion date	31/08/2021

Eligibility

Participant type(s)	Healthy volunteer
Age group	Adult
Sex	Female
Target sample size at registration	672
Total final enrolment	1232
Key inclusion criteria	Primipara, monoembryonic pregnancy (≤15 weeks of amenorrhoea for pregnant women to be supplemented)
Key exclusion criteria	1. IMC <17 and ≥ 30 but before pregnancy 2. Pregnant women suffering from calcium urinary lithiasis, renal failure, poorly controlled hypertension, unbalanced diabetes (fasting blood sugar >7 mmol/l or blood sugar >11 mmol/l), hypercalcemia (>2.65 mmol/l) and other phosphocalcic pathologies, bone diseases, lithium intake, digestive malabsorption
Date of first enrolment	01/03/2020
Date of final enrolment	31/03/2021

Locations

Countries of recruitment

Congo, Democratic Republic

Study participating centres

Hopital Provincial Du Nord-Kivu

-
Congo, Democratic Republic

Hgr Charite Maternelle

-
Congo, Democratic Republic

Hopital De Panzi

-
Congo, Democratic Republic

Hopital De Kyeshero

-
Congo, Democratic Republic

Hopital Heal Africa

-
Congo, Democratic Republic

Hopital De Mwesso

-
Congo, Democratic Republic

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request at the end of the study according to the sharing policy of the university. The researchers will treat this data in strict anonymity when it is published.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		03/02/2024	09/02/2024	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

09/02/2024: Publication reference added.
09/08/2022: The intention to publish date has been changed from 28/02/2022 to 28/02/2023.
26/01/2022: The intention to publish date has been changed from 31/01/2022 to 28/02/2022.
14/12/2021: The intention to publish date was changed from 31/12/2021 to 31/01/2022.
01/07/2021: Total final enrolment number added.
07/06/2021: The overall trial end date was changed from 30/06/2021 to 31/08/2021.
13/01/2021: Internal review.
16/11/2020: Trial's existence confirmed by the Ethics Committee of the University of Lubumbashi.