GOT-IT Trial: Glyceryl Trinitrate for Retained Placenta

NCT ID: NCT02085213

Last Updated: 2018-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2017-10-05

Brief Summary

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.

Detailed Description

Although a growing body of evidence supports a use for GTN for treatment of RP, much of this evidence is based on anecdotal case-reports or clinical "trials" which are non-randomised, do not include a placebo arm and are underpowered. Further, in the context of constrained maternity resources in a publicly funded health system, it is important to quantify the costs associated with the use of GTN (including any subsequent monitoring costs and costs associated with complications) in relation to its effectiveness and any subsequent cost savings it may deliver over standard practice. There is therefore an urgent need for a pragmatic clinical trial of GTN for RP to determine whether GTN is efficacious, safe, acceptable and cost-effective as a treatment for RP before a treatment which may (or may not) work is embedded within routine clinical practice. Our proposed randomised placebo controlled double blind pragmatic UK wide GOT-IT trial RCT (with internal pilot study) will definitively determine whether sublingual GTN is (or is not) clinically and cost effective for management of RP.

Conditions

Placenta, Retained

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Glyceryl Trinitrate

Nitrolingual Pump Spray [Coro-Nitro] A liquid within non-pressurised, red plastic-coated glass bottle fitted with a pump capable of delivering a metered dose containing 400μg of glyceryl trinitrate.

Excipients: The formulation contains fractionated coconut oil, absolute ethanol, medium chain partial glycerides and peppermint oil.

The treatment will be self administered (2 puffs) as a single intervention. No second intervention will be given.

Group Type: EXPERIMENTAL

Glyceryl Trinitrate

Intervention Type: DRUG

Placebo

Matched placebo formulation (except for active ingredient of Glyceryl Trinitrate) with matched packaging and labelling.

Group Type: PLACEBO_COMPARATOR

Matched Placebo

Intervention Type: DRUG

Matched placebo

Interventions

Glyceryl Trinitrate

Intervention Type: DRUG

Matched Placebo

Matched placebo

Intervention Type: DRUG

Other Intervention Names

GTN; Dummy treatment

Eligibility 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 in theatre
• 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.

• Minimum Eligible Age: 16 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Aberdeen

OTHER

Sponsor Role: collaborator

NHS Lothian

OTHER_GOV

Sponsor Role: collaborator

University of Edinburgh

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fiona C Denison, Dr

Role: PRINCIPAL_INVESTIGATOR

University of Edinburgh

Locations

Royal Infirmary of Edinburgh

Edinburgh, Midlothian, United Kingdom

Countries

United Kingdom

References

Denison FC, Carruthers KF, Hudson J, McPherson G, Chua GN, Peace M, Brewin J, Hallowell N, Scotland G, Lawton J, Norrie J, Norman JE; GOT-IT investigator team. Nitroglycerin for treatment of retained placenta: A randomised, placebo-controlled, multicentre, double-blind trial in the UK. PLoS Med. 2019 Dec 30;16(12):e1003001. doi: 10.1371/journal.pmed.1003001. eCollection 2019 Dec.

Reference Type: DERIVED

PMID: 31887169 (View on PubMed)

Other Identifiers

2013-003810-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

12/29/01

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

13/NE/0339

Identifier Type: OTHER

Identifier Source: secondary_id

HTA 12/29/01

Identifier Type: -

Identifier Source: org_study_id