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Placental growth fActor Repeat sampling for Reduction of adverse perinatal Outcomes in women with suspecTed pre-eclampsia: study protocol for a randomised controlled trial (PARROT-2)

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Alice Hurrell, Jenie Sparkes, Kate Duhig, Paul T Seed, Jenny Myers, Cheryl Battersby, Katherine Clark, Marcus Green, Rachael M Hunter, Andrew H Shennan, Lucy C Chappell, Louise Webster

Original languageEnglish
Article number722
Pages (from-to)481-487
Number of pages7
JournalTrials
Volume23
Issue number1
DOIs
Published2 Sep 2022

Bibliographical note

Funding Information: The trial is funded by Tommy’s Charity and the Jon Moulton Charitable Trust. Funding for PlGF-based tests was also received from the Biomedical Research Centre (BRC) and Roche. The study sponsor and funders have had no role in the design of this study and will have no role in its execution, analyses, interpretation of the data, or decision to submit results. Funding Information: None Oversight committees Project Management Group (PMG) The PMG will monitor the day-to-day running of the Trial and will meet on a regular basis (monthly) either in person or virtually. Members of the PMG will include: Prof Lucy Chappell (co-CI) Dr Louise Webster (co-CI) Dr Alice Hurrell (Trial Coordinator) Ms Jenie Sparkes (Senior Trial Midwife) Trial Steering Committee (TSC) The role of the TSC is to provide overall supervision of the study. The TSC will monitor the progress of the study and conduct and advise on its scientific credibility. The TSC will consider and act, as appropriate, upon the recommendations of the Data Monitoring Committee (DMC) and ultimately carries the responsibility for deciding whether the trial needs to be stopped on grounds of efficacy or safety. A TSC charter will be agreed upon at the first TSC meeting to document how the committee will operate. Members of the TSC are as follows: Dr Lucy Mackillop (Chair) Dr Christopher Gale Dr Kylie Watson Sarah Findlay Professor Lucy Chappell (Chief Investigator) A DMC independent of the applicants and the TSC will review the progress of the trial at least annually and provide advice on the conduct of the trial to the TSC. The committee will periodically review trial progress and outcomes. The timing and content of the DMC reviews are detailed in the DMC charter, agreed upon at the first DMC meeting, and completed following the recommendations of the DAMOCLES study [26]. The appointed members of the DMC are: Dr Katherine Tucker (Chair) Prof Basky Thilaganathan Dr Ushma Galal Mr Paul Seed (Trial statistician) The study is co-sponsored by King’s College London (KCL) and Guy’s and St Thomas’ NHS Foundation Trust. As co-sponsor, KCL has a specialist insurance policy in place which would operate in the event of any participant suffering harm as a result of their involvement in the research. Publisher Copyright: © 2022, The Author(s).

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Abstract

BACKGROUND: Pre-eclampsia is a complex pregnancy disorder, characterised by new or worsening hypertension associated with multi-organ dysfunction. Adverse outcomes include eclampsia, liver rupture, stroke, pulmonary oedema, and acute kidney injury in the mother, and stillbirth, foetal growth restriction, and iatrogenic preterm delivery for the foetus. Angiogenic biomarkers, including placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1), have been identified as valuable biomarkers for preterm pre-eclampsia, accelerating diagnosis and reducing maternal adverse outcomes by risk stratification, with enhanced surveillance for high-risk women. PlGF-based testing for suspected preterm pre-eclampsia has been incorporated into national guidance. The role of repeat PlGF-based testing and its effect on maternal and perinatal adverse outcomes have yet to be evaluated.

METHODS: The PARROT-2 trial is a multi-centre randomised controlled trial of repeat revealed PlGF-based testing compared to repeat concealed testing, in women presenting with suspected pre-eclampsia between 22+0 and 35+6 weeks' gestation. The primary objective is to establish whether repeat PlGF-based testing decreases a composite of perinatal severe adverse outcomes (stillbirth, early neonatal death, or neonatal unit admission). All women prior to enrolment in the trial will have an initial revealed PlGF-based test. Repeat PlGF-based tests will be performed weekly or two-weekly, depending on the initial PlGF-based test result, with results randomised to revealed or concealed.

DISCUSSION: National guidance recommends that all women presenting with suspected preterm pre-eclampsia should have a single PlGF-based test when disease is first suspected, to help rule out pre-eclampsia. Clinical and cost-effectiveness of repeat PlGF-based testing has yet to be investigated. This trial aims to address whether repeat PlGF-based testing reduces severe maternal and perinatal adverse outcomes and whether repeat testing is cost-effective.

TRIAL REGISTRATION: ISRCTN 85912420 . Registered on 25 November 2019.

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