The iSEARCH Trials of oral Sildenafil in labour: Protocol for a randomised trial in 3,200 Australian women and Rationale for an Individual Participant Data Prospective Meta-Analysis of trials in 14,000 women in high-income countries and a mega-trial of 50,000 women in low or middle-income countries.
Bibliographic record
Abstract
Abstract IntroductionWe showed in a Phase 2 RCT that oral Sildenafil during term labour halves the need for operative birth for suspected fetal distress. To assess if Sildenafil reduces adverse perinatal outcomes, we describe a Phase 3 RCT (iSEARCH) and the rationale for an individual participant data prospective meta-analysis (IPD PMA) of RCTs in high-income countries and a mega-trial in low- and middle-income countries.Methods and analysisiSEARCH will enrol 3200 women in term labour, yielding >80% power to determine whether oral administration of up to three 50 mg doses of Sildenafil versus placebo reduces the relative risk of intrapartum hypoxia, determined as a primary composite endpoint of ten perinatal outcomes, by 35% (from 7% to 4.55%). We also outline the rationale for (i) an IPD PMA of RCTs in about 14,000 women in Australia and other countries with low perinatal mortality rates which would yield 90% power to test if oral Sildenafil achieves a more moderate and realistic reduction of 20% in the relative risk of this composite endpoint and (ii) a mega-trial in about 50,000 women in countries with moderate or high perinatal mortality rates to test if oral Sildenafil achieves a similarly moderate and realistic 20% reduction in the relative risk of a composite endpoint comprising intrapartum stillbirth or 7-day neonatal mortality. Secondary aims will be to evaluate the rate of operative birth for fetal distress, its cost-effectiveness, and developmental and educational outcomes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.094 | 0.120 |
| Meta-epidemiology (narrow) | 0.007 | 0.004 |
| Meta-epidemiology (broad) | 0.012 | 0.017 |
| Bibliometrics | 0.003 | 0.004 |
| Science and technology studies | 0.003 | 0.004 |
| Scholarly communication | 0.006 | 0.005 |
| Open science | 0.003 | 0.003 |
| Research integrity | 0.010 | 0.011 |
| Insufficient payload (model declined to judge) | 0.038 | 0.011 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".