PRISM Progesterone in Spontaneous Miscarriage trial

Research at St Michael's Hospital Early Pregnancy Unit
Mrs Overton Primary Investigator
Funded by the National Institute for Health Research

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%. We will also explore the effects of progesterone in prognostic subgroups, according to maternal age, fetal heart activity, gestation at presentation, amount of bleeding and body mass index.

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.

We plan to randomise 4150 women in total (2075 participants each in the progesterone and placebo arms)

The primary objective is to test the hypothesis that in women presenting with vaginal bleeding in the first 12 weeks, progesterone (400 mg vaginal capsules, twice daily), started as soon as possible after a scan has demonstrated a visible intrauterine gestation sac  and continued  to 16 completed weeks of gestation, compared with placebo, increases maternities with live births beyond 34 completed weeks by at least 5%.

The secondary objectives are to test the hypothesis that progesterone improves other pregnancy and neonatal outcomes, including gestation at birth and survival at 28 days neonatal life.

To test the hypothesis that progesterone, compared with placebo, Is not associated with serious adverse effects to the mother or the neonate, including chromosomal anomalies in the newborn.

To explore differential or subgroup effects of progesterone in this prognostic subgroups, including age, fetal heart activity, gestation at presentation, amount of bleeding and body mass index.

To perform a cost effectiveness analysis, with cost per additional birth over 34 weeks' gestation from an NHS and Personal Social Services perspective as the primary analysis.  We will also model longer term outcomes to the extent of the data permit.

Who can take 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.