PRISM Progesterone in Spontaneous Miscarriage trial
Research at St Michael's Hospital Early Pregnancy Unit
Mrs Overton Primary Investigator at St Michaels University hospitals Bristol Early Pregnancy Assessment Clinic.
Funded by the National Institute for Health Research
Published in the New England Journal of Medicine May 2019
The PRISM trial is a large, double-blind, placebo-controlled trial to test the hypothesis that in women presenting with vaginal bleeding in the first 12 weeks, progesterone (400 milligram vaginal capsules, twice-daily), started as soon as possible after a scan has demonstrated a visible intrauterine gestation sac and continue to 16 completed weeks of gestation, compared with placebo, increases maternities with live births beyond 34 completed weeks by at least 5%.
Should the PRISM trial demonstrate a significant benefit from the intervention, it would represent a major breakthrough in the treatment of this common and distressing condition. Given that progesterone treatment is cheap, safe and convenient, and the financial impact of miscarriage substantial, even a small improvement in outcome is likely to be cost-effective.
Who took part?
- Women age 16-39 who present with bleeding in the first 12 weeks of pregnancy.
- Who have an intrauterine gestation sac visible on ultrasound
- Are willing to be selected at random to have either the treatment or placebo, without knowing which they are given.
- Who are not already taking progesterone supplementation
- Who do not have contraindications to progesterone therapy
- Who are not already taking part in any other blinded, placebo-controlled controlled trials of drugs in pregnancy.
A total of 4153 women were recruited at 48 hospitals in the UK, and randomly assigned to receive progesterone (2079 women) or placebo (2074 women).? Data was available for 4038 of 4153 women.
The incidence of live births after 34 weeks of pregnancy was 75% (1513/2025 women) in the progesterone group and 72% (1459/2013 women) in the placebo group. The 3% difference in live birth was not statistically significant, meaning that the difference could be due to chance.? The incidence of adverse events did not differ significantly between the groups.?
However, when the results were split by number of previous miscarriages, the analysis showed that in women with
- No previous miscarriages the live birth rate was 74% (824/1111) in the progesterone group and 75% (840/1127) in the placebo group i.e. no benefit
- 1-2 previous miscarriages the live birth rate was 76% (591/777) in the progesterone group and 72% (534/735) in the placebo group i.e. some benefit
- 3 or more previous miscarriages the live birth rate was 72% (98/137) in the progesterone group and 57% (85/148) in the placebo group i.e. substantial benefit
The results of the study suggests that women with bleeding in early pregnancy with a history of previous miscarriage could benefit from progesterone treatment has huge implications.? This treatment could save thousands of babies who may otherwise have been lost to miscarriage.?
A study evaluating the economic implications of the PRISM trial published in the British Journal of Obstetrics & Gynaecology concludes that progesterone is also cost-effective, costing on average ?204 per pregnancy.