Simplified treatment for eclampsia prevention using magnesium sulfate: a phase III, randomised, open label, active controlled, multicountry, multicentre, non-inferiority trial of simplified magnesium sulfate regimen for eclampsia prophylaxis
Prevention of eclampsia in patients with pre-eclampsia
Experimental arm Women in the intervention arm will receive the simplified regimen of two IM doses of 10g magnesium sulphate 12 hours apart. Active control arm Women in the active control arm will receive either the standard IV (Zuspan) regimen consisting of IV injection of 4 g over 10-15 minutes as a loading dose, followed by a maintenance IV infusion of 1 g per hour for 24 hours (total dose 28g); or standard IM (Pritchard) regimen consisting of IV injection of 4 g over 10-15 minutes and IM injection of 10g as a loading dose, followed by a maintenance IM injection of 5 g every 4 hours for 24 hours (total dose 39g). Participants will be randomly assigned to either experimental or standard arms (allocation ratio of 1:1) as per a computer-generated randomization sequence in permuted blocks. All sites will receive identical treatment packs; each pack will contain the required number of magnesium sulfate ampoules for the simplified or standard regimen according to the randomization sequence. The packs will be assembled consecutively in special dispensers with slots at the lower end where treatment packs can be removed sequentially. The treatment packs will be used in the order in which they are removed through the slot in the dispenser to maintain the randomization sequence. The assignment schedule will be stored at the WHO headquarters. After signing the informed consent, trained study staff will randomize a woman by taking the next numbered treatment pack from the dispenser. Women will be randomized to receive either the simplified IM regimen of 10g IM administered 12 hourly x 2 doses or either standard Zuspan or Pritchard regimen, depending on the designated treatment protocol in the participating hospitals. Study participants and personnel will not be blinded to the group allocation due to the nature of study interventions.
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 mmHg, or diastolic blood pressure ≥110 mmHg 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.
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.