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.: PACTR202112816270738 Date of Approval: 07/12/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title The STEP-Mag Trial
Official scientific title Simplified Treatment for Eclampsia Prevention using Magnesium sulfate: A phase III, randomized, open label, active-controlled, multicountry, multicentre, non-inferiority trial of simplified magnesium sulfate regimen for eclampsia prophylaxis.
Brief summary describing the background and objectives of the trial Background and Objectives Burden of hypertensive disorders of pregnancy Pre-eclampsia and eclampsia are the second leading causes of maternal mortality globally.They dominate hypertensive disorders of pregnancy, which are responsible for close to one-tenth of maternal deaths in Asia and Africa and about a quarter of maternal deaths in Latin America. They are also recognized causes of severe maternal morbidity and long-term disability for both mothers and their babies. Although the relative incidence of pre-eclampsia is comparable between countries worldwide, low- and middle-income countries carry a disproportionately larger share of the associated complications and poor outcomes. For instance, while eclampsia occurs in about 1 in 2000 deliveries in the United Kingdom and other high-income countries, it occurs in 1 in 100 to 1700 deliveries in low-income countries. Magnesium sulfate is widely accepted as a life-saving drug for preventing progression of pre-eclampsia to eclampsia and avoiding associated complications.6 There is compelling evidence that it halves the risk of eclampsia and probably reduces the risk of maternal mortality in women with pre-eclampsia. Primary objective The primary objective of this trial is to evaluate non-inferiority of magnesium sulfate 10g IM administered 12 hourly x 2 doses compared with a standard IV (Zuspan) or IM (Pritchard) magnesium sulfate regimen in the prevention of maternal eclamptic seizure. Secondary objective The secondary objective of this trial is to evaluate the superiority of magnesium sulfate 10g IM administered 12 hourly x 2 doses compared with a standard IV (Zuspan) or IM (Pritchard) magnesium sulfate regimen in the proportion of women experiencing adverse events indicative of magnesium toxicity.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Obstetrics and Gynecology,Pregnancy and Childbirth
Sub-Disease(s) or condition(s) being studied Preeclampsia
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/03/2022
Actual trial start date
Anticipated date of last follow up 29/02/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 12000
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
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 Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Magnesium Sulphate two doses of 10 g 12 hours apart Anticonvulsant 6000
Control Group Magnesium sulphate 1. Standard IV (Zuspan) regimen IV 4 g over 10-15 minutes as a loading dose, followed by a maintenance IV infusion 1 g per hour for 24 hours (total dose 28g); or 2. Standard IM (Pritchard) regimen IV injection 4 g over 10-15 minutes and IM injection of 10g loading dose, followed by a maintenance IM injection of 5 g every 4 hours for 24 hours (total dose 39g). Zuspan- 24 hours Pritchard- 24 hours (total dose 39g) Antionvulsant 6000 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
To be eligible for inclusion into this trial, the women must fulfill all of the following criteria: 1. Be admitted with a diagnosis of pre-eclampsia and with clinical or laboratory indication(s) for magnesium sulfate treatment, as defined by any of the following: two readings of systolic blood pressure ≥160 mm Hg, or diastolic blood pressure ≥110 mm Hg along with ≥2+ proteinuria on urine dipstick; or the presence of symptoms, signs or laboratory findings suggestive of severe disease such as headache, visual disturbances, upper abdominal pain, pulmonary oedema, nausea and vomiting, hyperreflexia or clonus, elevated liver enzymes, raised serum creatinine, or thrombocytopenia. Women with HELLP syndrome, a severe form of pre-eclampsia characterized by Haemolysis, Elevated Liver enzymes, and Low Platelets (<100 cells/mcl) will be included if there is no clinical contraindication to IM injection. 2. Have not yet given birth but birth is planned or expected within the next 24 hours, or have given birth within the last 24 hours. 3. Provide written informed consent before any trial-related procedures are carried out. Women are not eligible if they fulfill any of the following exclusion criteria: 1. Unable or unwilling to give informed consent (because the woman is too distressed or not capable to understand, confirm and give informed consent due to emergency or health condition, or does not wish to be randomized for whatever reason). 2. Are non-emancipated minors (as per local regulations) without a guardian. 3. History of hypersensitivity to magnesium sulfate. 4. Serious cardiovascular disorders (WHO classification III or IV or acute heart failure). 5. Serious hepatic (encephalopathy or coma) or renal disease. 6. History of epilepsy. 7. Myasthenia gravis or any muscular dystrophies. 8. Coagulopathy. 9. Have previously received magnesium sulfate for eclampsia prevention in the current pregnancy. 10. Planned to receive magnesium sulfate regimen other than the regimens specified for the trial on account of other medical indication(s) (e.g. fetal neuroprotection). 11. Known oliguria (<400mL urine in 24 hours) at the time of admission. Adult: 19 Year-44 Year 16 Year(s) 49 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 05/10/2021 KNH UON ERC
Ethics Committee Address
Street address City Postal code Country
Kenyatta National Hospital Nairobi 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Maternal eclamptic seizure (defined as occurrence of convulsions in a woman with features of pre-eclampsia that is unrelated to other neurological conditions) N/A
Secondary Outcome Composite endpoint describing events related to maternal toxicity and consisting of one or more of the following: absent/reduced tendon reflexes, respiratory depression, use of calcium gluconate to combat perceived/confirmed maternal toxicity, or stopping/reduced magnesium sulfate treatment due to perceived/confirmed maternal toxicity N/A
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Nakuru Level 5 Hospital Showground road Nakuru 20100 Kenya
Mama Lucy Hospital Kangundo Road Nairobi 00515 Kenya
Naivasha District Hospital Lake view Naivasha 20117 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
WHO 20 Avenue Appia 1211 Geneva Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor World Health Organization 20 Avenue Appia 1211 Geneva Switzerland Funding Agency
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Zahida Qureshi zahida@qureshi.co.ke +254721310750 Old Mbagathi Road
City Postal code Country Position/Affiliation
Nairobi Kenya Associate Professor
Role Name Email Phone Street address
Public Enquiries Omondi Ogutu oomogutu@gmail.com +254722510215 Old Mbagathi Road
City Postal code Country Position/Affiliation
Nairobi Kenya Associate Professor
Role Name Email Phone Street address
Scientific Enquiries Alfred Osoti alfredos@uonbi.ac.ke +254733886664 Old Mbagathi Road
City Postal code Country Position/Affiliation
Nairobi Kenya Associate Professor
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Once the trial is completed and primary results published, this data set will be available for study partners and collaborators to use for further analyses. Informed Consent Form,Study Protocol Once the study is completed To be availed at a later date
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