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Chappell LC, Bell JL, Smith A, et al. Ursodeoxycholic acid to reduce adverse perinatal outcomes for intrahepatic cholestasis of pregnancy: the PITCHES RCT. Southampton (UK): NIHR Journals Library; 2020 Dec. (Efficacy and Mechanism Evaluation, No. 7.9.)

Chapter 2PITCHES mechanistic studies (led by Professor Catherine Williamson and Dr Peter H Dixon)

Introduction

The initial PITCHES award included partial funding for technical support at three sites (St Thomas’, Queen Charlotte’s and Chelsea, and Nottingham City Hospitals) to collect serum, urine and placental samples from trial participants. This was to facilitate the stated secondary objective of the study, namely to establish a biobank of samples to enable mechanistic studies to be undertaken to elucidate the mechanism of action of UDCA. Subsequently, through a variation to contract (VTC), some additional funding (£35,151) was provided to facilitate the collection of fetal heart rate data (using the Monica AN24 device; Monica Healthcare Ltd, Nottingham, UK) from trial participants.

Major milestones

PITCHES-M: sample collection for the mechanistic studies –

  • St Thomas’ and Queen Charlotte’s and Chelsea Hospitals have been open for these studies since the PITCHES trial began, with ethics approval under an existing research protocol (‘Obstetric Cholestasis (OC) Research Study’).
  • Nottingham City Hospital started recruiting in January 2018.

The set-up for the bile acid effects on fetal arrhythmia study (BEATS) is shown below in Table 13.

Recruitment report

The numbers of participants and samples is shown in Table 14.

As Professor Williamson also has approval to collect samples from a Wellcome Trust grant and for BEATS from a Tommy’s Charity grant, 407 additional non-PITCHES ICP participants have been recruited to the OC Research Study at St Thomas’ (205 women), Queen Charlotte’s and Chelsea (155 women), and Nottingham City (47 women) Hospitals. Since the VTC for BEATS was approved, 24 non-PITCHES ICP participants have been recruited to the fetal electrocardiogram (ECG) studies (14 at St Thomas’, six at Queen Charlotte’s and Chelsea, and three at Nottingham City Hospitals).

Safety reporting

There were no serious adverse events in either the PITCHES-M study or BEATS.

Discontinuations/withdrawals

There have been no discontinuations or withdrawals from the mechanistic studies.

Ongoing studies

As we were funded to collect only a biobank and fetal ECG traces, it will be necessary to apply for additional funds to generate research data from any of the samples. A request for use of the grant underspend was made, but declined as the work was hypothesis-generating rather than hypothesis-testing.

Tables

TABLE 13

Site opening for fetal ECG studies (BEATS)

HospitalEthics approvalR&D approvalSIVGreen lightFirst participantNotes
St Thomas’ HospitalPre September 2017Pre September 2017Pre September 20177 February 2018September 2017
Queen Charlotte’s and Chelsea HospitalPre September 2017Pre September 2017Pre September 20177 February 2018September 2017
Nottingham City Hospital21 November 201728 February 201817 January 201828 February 2018May 2018
Nottingham – Queen’s Medical Centre21 November 201728 February 201817 January 201828 February 2018NANever recruited
Western Sussex Hospitals NHS Trust21 November 201720 March 20187 November 201720 March 2018Post PITCHES
Warrington Hospital21 November 201720 April 20187 November 201720 April 2018NAStaff member on extended leave – unable to recruit
Norfolk and Norwich University Hospital21 November 2017–7 November 2017–NAReduced capacity at site – unable to recruit
Sunderland Royal Hospital21 November 2017–7 November 2017–NAR&D did not have capacity to work on study
St George’s Hospital21 November 2017–7 November 2017–NAR&D never confirmed capacity and capability

NA, not applicable; R&D, Research and development; SIV, site initiation visit.

TABLE 14

Participants and samples in the PITCHES-M study and BEATS

HospitalTotal
St Thomas’Queen Charlotte’s and ChelseaNottingham City
PITCHES-M participants, n439658
PITCHES-M samples, n983614148
 Maternal blood3110445
 Maternal urine278439
 Maternal faeces3306
 Placenta127322
 Umbilical cord blood127019
 Meconium131317
Total number (number post VTC) of PITCHES–BEATS fetal ECG traces17 (7)3 (2)1 (1)21 (10)
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