GOT-IT Trial: Glyceryl Trinitrate for Retained Placenta

Condition(s) targeted: Retained Placenta.

Intervention: Glyceryl Trinitrate (Drug); Matched Placebo (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: University of Edinburgh

Official(s) and/or principal investigator(s):
Fiona C Denison, Dr, Principal Investigator, Affiliation: The University of Edinburgh

Overall contact:
Fiona C Denison, Dr, Phone: 0131 242 6449, Email: fiona.denison@ed.ac.uk

A retained placenta (RP) is a complication after a normal birth, which affects nearly 11,000 women in the UK per year. This is where the placenta is not delivered spontaneously after giving birth. It is a major cause of postpartum haemorrhage (major loss of blood) which can

lead to the death of the mother. The recommended treatment for RP is a surgical procedure -

manual removal of placenta (MROP). This is a painful and unpleasant intervention for the women, involving additional hospital stay, and is an expensive outcome for the NHS. It is widely recognised that non-surgical management options for RP are limited and it has been recommended that research is needed into new medical treatments for RP. New effective treatments for RP would dramatically reduce the number of women requiring MROP with the operation being restricted to the small minority of women with particularly stuck placentae. The reduction in operative interventions would have cost benefits for the NHS and also for women in terms of increased satisfaction, less separation of mother and baby immediately after birth, and reduced morbidity. This study will try to prove the clinical and cost effectiveness of a known treatment for angina, Glyceryl trinitrate (GTN) used to treat RP. The investigators will compare GTN against a placebo (dummy treatment) in a randomised controlled blinded trial (GOT-IT). The GOT-IT Trial will be conducted in two phases. The first phase will involve an internal pilot study where the aim will be to test out and refine trial procedures in a small number of hospital sites. The second phase will be the main trial where recruitment will be extended to a larger number of hospitals in order to determine clinical and cost effectiveness.

Official title: GOT-IT Trial: A Pragmatic Group Sequential Placebo Controlled Randomised Trial to Determine the Effectiveness of Glyceryl Trinitrate for Retained Placenta.

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Need for Manual Removal of Placenta

Blood Loss

Satisfaction with treatment

Net incremental costs (or cost savings) to the National Health Service

Secondary outcome:

Fall in haemoglobin

Time from randomisation to delivery of placenta.

Need for Manual Removal of Placenta in theatre.

Need for earlier than planned MROP on the basis of the clinical condition.

Systolic and diastolic blood pressure.

Need for blood transfusion

Need for general anaesthesia

Maternal Pyrexia

Sustained uterine relaxation.

Mean costs for each treatment allocation group

Minimum age: 16 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Women with retained placenta.

- Women aged 16 or over.

- Women with vaginal delivery (including women with a previous caesarean section).

- Haemodynamically stable (systolic blood pressure more than 100mg Hg and pulse less

than 110 beats per min).

- > 14 weeks gestation.

Exclusion Criteria:

- Unable to give informed consent.

- Suspected placenta accreta/increta/percreta.

- Multiple pregnancy.

- Women having an instrumental vaginal delivery.

- Allergy or hypersensitivity to nitrates or any other constituent of the formulation.

- Taken alcohol in the last 24 hours.

- Concomitant use with phosphodiesterase inhibitors (such as sildenafil, tadalafil, or

vardenafil).

- Contra-indication due to one of the following: Severe anaemia, constrictive

pericarditis, extreme bradycardia, incipient glaucoma, Glucose-6- phosphatedehydrogenase-deficiency, cerebral haemorrhage and brain trauma, aortic and / or mitral stenosis and angina caused by hypertrophic obstructive cardiomyopathy. Circulatory collapse, cardiogenic shock and toxic pulmonary oedema.

- Currently participating in another CTIMP.

Fiona C Denison, Dr, Phone: 0131 242 6449, Email: fiona.denison@ed.ac.uk

Royal Infirmary of Edinburgh, Edinburgh, Midlothian EH16 4TJ, United Kingdom; Recruiting
Fiona C Denison, Dr, Principal Investigator

Starting date: September 2014
Last updated: December 2, 2014