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The Must-Read Trial: Eclampsia

Every so often comes along a trial report which comes into the "must-read" category. It can be a super design, or an important result, or often both.

One such is the recent Lancet report of the Collaborative Eclampsia trial from Lelia Duley [1].

How big is the problem?

Eclampsia is the occurrence of one or more convulsions in association with the syndrome of pre-eclampsia. It is relatively uncommon in developed counties where it complicates about one in every 2,000 deliveries. Eclampsia can be 20 times more common in developing countries, and it probably accounts for more than 50,000 maternal deaths world-wide each year.

What is the question?

What should be used to treat the convulsions? Diazepam, phenytoin and magnesium sulphate have and are being used.

The Collaborative Eclampsia Trial was set up to determine which, if any, is superior. There were nearly 1,700 women randomised to treatments in two separate trials - magnesium sulphate against diazepam and magnesium sulphate against phenytoin.

For the trial of magnesium sulphate against diazepam 910 women were randomised in 23 centres in eight countries - Argentina, Brazil, Colombia, Ghana, India, Uganda, Venezuela and Zimbabwe. For the trial of magnesium sulphate against phenytoin 777 women were randomised in four centres in South Africa and India.

All women with a clinical diagnosis of eclampsia were eligible, with the only exclusions was if a study drug was contraindicated.

Treatments

Magnesium sulphate was given as an intravenous loading dose followed by intravenous infusion or intramuscular injections for 24 hours. Diazepam was given as an intravenous loading dose followed by an intravenous infusion for 24 hours. Phenytoin was given as a slow intravenous infusion followed by further intravenous doses every six hours for 24 hours.

Outcomes

The primary outcomes were recurrence of convulsions and maternal death. There were other secondary outcomes - though these are not commented on here.

Results

Magnesium sulphate was superior to diazepam; significantly fewer recurrences of fits occurred with magnesium sulphate (60/453) than with diazepam (126/452). The relative risk was 0.48 (95%CI 0.4 - 0.6). The reduction in maternal death (17/453 compared with 23/452) was not significant.

Magnesium sulphate was superior to phenytoin; significantly fewer recurrences of fits occurred with magnesium sulphate (22/388) than with diazepam (66/387). The relative risk was 0.33 (95%CI 0.2 - 0.5). The reduction in maternal death (10/388 compared with 20/387) was not significant.

Numbers-needed-to-treat

This was a comparison of medicines which were thought to be effective - but asking the question which was best. The NNT for magnesium sulphate against diazepam was 7 (5 - 11). The NNT for magnesium sulphate against phenytoin was 9 (6 - 14). Thus treating every eight women with eclampsia with magnesium sulphate rather than diazepam or phenytoin results in one fewer case of recurrent fits.

Conclusions

To conduct a large multicentre study across three continents, and to do it so beautifully, is a rare event. To do it well, and to produce such clear cut results, is exceptional. This is a classic study - and one to treasure.

Reference:

  1. L Duley. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet 1995 345: 1455-63.



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