Women’s Health · Clinical trials
Pre-eclampsia Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About pre-eclampsia — and why its trials are hard
Pre-eclampsia is a pregnancy-specific, multisystem hypertensive disorder - typically new-onset hypertension after 20 weeks with proteinuria or end-organ dysfunction - driven by abnormal placentation and an anti-angiogenic imbalance (elevated sFlt-1 relative to placental growth factor). It is a leading cause of maternal and perinatal morbidity and mortality worldwide, capable of progressing to eclampsia, HELLP syndrome, stroke and fetal growth restriction. Critically, there is NO approved disease-modifying drug: delivery of the placenta remains the only definitive cure, so management balances maternal stabilisation against fetal maturity. Current pharmacology is preventive or supportive rather than curative. Low-dose aspirin, validated by the ASPRE trial, reduces preterm pre-eclampsia in high-risk women when started early. Magnesium sulfate is the standard for eclampsia seizure prophylaxis and treatment, and antihypertensives (labetalol, nifedipine, hydralazine) control severe hypertension. Antenatal corticosteroids support fetal lung maturity before indicated preterm delivery. A long list of candidate therapeutics has failed, underscoring an enormous unmet need for treatments that prolong pregnancy safely.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| Low-dose aspirin (Aspirin (generic)) | N/A (established via evidence and guidelines; not an FDA disease-modifying approval) | Prevention of preterm pre-eclampsia in high-risk pregnancies (started early, typically before 16 weeks) | ASPRE (Rolnik et al., NEJM 2017) | Incidence of preterm pre-eclampsia (delivery before 37 weeks with pre-eclampsia) | Preterm pre-eclampsia in 1.6% (aspirin 150 mg) vs 4.3% (placebo); odds ratio 0.38 (~62% relative reduction, P=0.004) |
| Magnesium sulfate (Magnesium sulfate (generic)) | N/A (standard of care; not a disease-modifying approval) | Seizure prophylaxis in severe pre-eclampsia and treatment of eclampsia | Magpie Trial (Lancet 2002) and Collaborative Eclampsia Trial | Incidence of eclampsia (seizures) | Magpie: >50% reduction in eclampsia risk vs placebo (relative risk ~0.42); superior to phenytoin/diazepam for treating eclampsia |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in pre-eclampsia development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Sildenafil (phosphodiesterase-5 inhibitor) — STRIDER (Dutch arm; Groom et al., published 2018) | Trial stopped early; no benefit for fetal growth in pre-eclampsia/growth restriction and a safety signal | Excess neonatal deaths attributed to persistent pulmonary hypertension of the newborn in the sildenafil arm; harm outweighed any benefit |
| Pravastatin — StAmP (UK) and related statin prevention trials | Did not significantly lower sFlt-1 or alter pre-eclampsia course | Underpowered results and no clear reduction in circulating anti-angiogenic factors or clinical progression; effect not established |
| Esomeprazole (proton pump inhibitor) — PIE trial (South Africa; Cluver et al., 2018) | Did not prolong pregnancy or improve outcomes in preterm pre-eclampsia | Despite preclinical sFlt-1-lowering rationale, no clinical benefit in prolonging gestation was seen versus placebo |
| Vitamin C and vitamin E (antioxidants) — VIP trial (Lancet 2006) and related antioxidant trials | No reduction in pre-eclampsia; potential signal of harm (low birth weight) | The oxidative-stress hypothesis did not translate to prevention, and supplementation was associated with adverse outcomes |
Choosing the right endpoint
Primary endpoints that matter in pre-eclampsia trials
- Incidence of (preterm) pre-eclampsia — Primary prevention endpoint used in trials such as ASPRE; preterm disease carries the greatest morbidity
- Eclampsia (seizures) — Key outcome for magnesium sulfate prophylaxis and treatment trials
- Composite maternal morbidity — Includes severe hypertension, HELLP, renal/hepatic dysfunction, stroke and maternal death
- Prolongation of pregnancy / gestational age at delivery — Central goal of any hoped-for disease-modifying therapy, given delivery is currently the only cure
- Adverse perinatal outcome — Composite of fetal growth restriction, stillbirth, neonatal death and NICU morbidity
How iNGENū runs pre-eclampsia trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Pre-eclampsia clinical trials — FAQs
Is there a drug that cures pre-eclampsia?
Who should take low-dose aspirin?
What does magnesium sulfate do?
Ready to discuss your pre-eclampsia trial?
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