Concurrent Session 4D - Maternal Fetal Medicine - Can we embed national megatrials in care to test if Viagra in term labour reduces perinatal mortality?
Friday, February 14, 2020
3:30 PM – 4:00 PM
Location: Max Bell Auditorium
Professor William Tarnow-Mordi graduated with first class Honours in medicine in Cambridge, UK, and completed specialist neonatal training in Oxford. He moved from Dundee to Sydney in 1999 to become Director of Neonatal and Perinatal Trials at the NHMRC Clinical Trials Centre. He leads a research program in larger-scale RCTs with successful funding from NHMRC for INIS,1 BOOST-II,2 APTS,3 LIFT, LEAP, TORPIDO-2 and ESPRESSO and from the Australian Medical Research Future Fund for WHEAT- all major phase III trials that have had or will have a significant influence on international clinical practice. He was awarded the Australian Clinical Trials Alliance (ACTA) Clinical Trial of Year 1st Runner Up (2017) for BOOST-II; ACTA Trial of the Year (2018) for APTS and co-awarded the ACTA Consumer Award (2019) with Melinda Cruz, a parent investigator, for TORPIDO3060.
He will draw lessons from the (many) limitations of perinatal trials and meta-analyses addressing how to reduce mortality or morbidity with antenatal antibiotics through the ORACLE trials,4,5 aspirin through the PARIS COllaboration,6,7 delayed clamping of the umbilical cord,8 targeting safe oxygen saturation levels in preterm babies9 and – most recently – by giving women in labour at term oral Sildenafil (Viagra) to reduce Caesarean section and emergency instrumental birth for fetal distress through the RIDSTRESS Phase II trial.10 Can we improve disability or morbidity-free survival in a new generation of international trials which can enrol tens of thousands of participants, ten times faster, a tenth of current costs? He will invite the critical engagement and wholehearted support of Canadian colleagues, firstly in considering participation in iSEARCH - a proposed series of international Phase III megatrials of Viagra in term labour - and secondly in helping to build a global initiative to transform healthcare - starting with perinatal medicine - by embedding key trials into routine care through the ENRICH (Embedding Necessary Research In Culture and Health) Initiative, coordinated through the ALPHA Collaboration for Advancing Large, collectively Prioritized trials of Health outcomes Assessment.
1. Brocklehurst P, et al. Treatment of neonatal sepsis with intravenous immune globulin. NEJM 2011;365:1201-11.
2. Tarnow-Mordi W, Stenson B, Kirby A, et al. BOOST II Australia and BOOST II UK Collaborative Study Groups. Outcomes of Two Trials of Oxygen-Saturation Targets in Preterm Infants. N Engl J Med 2016;374:749-60.
3. Tarnow-Mordi W, et al. Delayed versus Immediate Cord Clamping in Preterm Infants. NEJM 2017;377:2445-55.
4. Kenyon SL, Taylor DJ, Tarnow-Mordi W. Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. ORACLE Collaborative Group. Lancet 2001;357:979-88.
5. Kenyon SL, Taylor DJ, Tarnow-Mordi W. Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. ORACLE Collaborative Group. Lancet 2001;357:989-94.
6. Askie LM, Duley L, Henderson-Smart DJ, Stewart LA, Group PC. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet 2007;369:1791-8.
7. Hoffman MK, et al. Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial. Lancet 2020;395:285-93.
8. Fogarty M, Osborn DA, Askie L, et al. Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis. Am J Obstet Gynecol 2018;218:1-18.
9. Askie LM, Darlow BA, et al. Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA 2018;319:2190-201.
10. Turner J, Dunn L, Tarnow-Mordi W, et al. Safety and efficacy of sildenafil citrate to reduce operative birth for intrapartum fetal compromise at term: A Phase 2 Randomized Controlled Trial, American Journal of Obstetrics and Gynecology (2020), doi: https://doi.org/10.1016/j.ajog.2020.01.025 accessed 31 Jan 2020. [See overleaf for learning objectives]
* give examples of the inequity in the availability of reliable evidence of moderate treatment benefits to caregivers from adequately powered trials in adult versus perinatal medicine
* construct or interpret a table of sample sizes for trials powered to show moderate benefits in disability-free survival reliably using www.sealedenvelope.com or a similar online calculator
* demonstrate why international collaboration is essential to achieve large scale randomised evidence with sufficient power to evaluate the impact of promising interventions (such as Viagra in term labour) on perinatal mortality
* endorse or contribute to the development of the ALPHA Collaboration for Advancing Large collectively Prioritized trials of Health outcomes Assessment and the ENRICH Initiative to Embed Necessary Research Into Culture and Health