GOT-IT Trial: Glyceryl Trinitrate for Retained Placenta

NCT02085213 | Completed Phase 4 DMC

• 4 other identifiers: HTA 12/29/012013-003810-4212/29/0113/NE/0339
• Study Type: interventional
• Target: 1,107
• Locations: 1 country
• Sites: 1

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.

Conditions

Placenta, Retained

Keywords

Retained placenta; Manual Removal of Placenta; Glyceryl Trinitrate

Outcome Measures

Primary Outcomes (1)

• Need for Manual Removal of Placenta

  Defined as the placenta remaining undelivered 15 minutes post study treatment and/or being required within 15 minutes of treatment due to safety concerns.

  From time of randomisation up to 15-minutes post administration of study treatment

Secondary Outcomes (9)

• Fall in haemoglobin

  First postnatal day (approximately 24 hours since the birth).

• Time from randomisation to delivery of placenta.

  From time of randomisation and administration of the study treatment to delivery of placenta (up to approximately 2 hours).

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

  From time of randomisation and administration of the study treatment to delivery of placenta (up to approximately 2 hours).

• Systolic and diastolic blood pressure.

  Study treatment to 15 minutes postadministration.

• Need for blood transfusion

  From the time of delivery of the placenta to time of discharge from hospital (up to 7 days).

Study Arms (2)

Glyceryl Trinitrate

EXPERIMENTAL

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.

Drug: Glyceryl Trinitrate

Placebo

PLACEBO COMPARATOR

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

Drug: Matched Placebo

Interventions

Glyceryl Trinitrate DRUG

Also known as: GTN

Glyceryl Trinitrate

Matched Placebo DRUG

Matched placebo

Also known as: Dummy treatment

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Edinburgh: lead
• University of Aberdeen: collaborator
• NHS Lothian: collaborator

Study Sites (1)

Royal Infirmary of Edinburgh

Edinburgh, Midlothian, EH16 4TJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31887169 DERIVED

MeSH Terms

Conditions

Placenta, Retained

Interventions

Nitroglycerin

Condition Hierarchy (Ancestors)

Placenta Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Nitro Compounds; Organic Chemicals

Study Officials

• Fiona C Denison, Dr

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2014
• First Posted: March 12, 2014
• Study Start: September 1, 2014
• Primary Completion: July 26, 2017
• Study Completion: October 5, 2017
• Last Updated: May 21, 2018

Record last verified: 2018-05

Locations

GB (1)