Placenta, RetainedPhase 4GOT-ITNCT02085213
GOT-IT Trial: Glyceryl Trinitrate for Retained Placenta
A Phase 4 study testing Glyceryl Trinitrate in people with Placenta, Retained, run by University of Edinburgh at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older, women only
- Conditions the study is for
- Placenta, Retained
- What is being tested?
- Glyceryl Trinitrate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,107 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2014to 5 Oct 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Infirmary of Edinburgh
Edinburgh, Midlothian, EH16 4TJ
About this study
Official title: GOT-IT Trial: A Pragmatic Group Sequential Placebo Controlled Randomised Trial to Determine the Effectiveness of Glyceryl Trinitrate for Retained Placenta.
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.
Read the 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
- Being tested
- Glyceryl Trinitrate, Matched Placebo
- Keywords
- Retained placenta, Manual Removal of Placenta, Glyceryl Trinitrate
- Medical subject headings
- Placenta, Retained
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glyceryl TrinitrateDrug
Also called GTN
Matched PlaceboDrug
Also called Dummy treatment
Matched placebo
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Glyceryl Trinitrate |
| Placebo | Placebo comparator | Matched placebo formulation (except for active ingredient of Glyceryl Trinitrate) with matched packaging and labelling. Receives: Drug: Matched Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From time of randomisation up to 15-minutes post administration of study treatment
Secondary outcomes (9)
Fall in haemoglobin
Fall in haemoglobin of more than 15% between recruitment and the first postnatal day.
Measured: First postnatal day (approximately 24 hours since the birth).
Time from randomisation to delivery of placenta.
The time from when the study drug is administered until the placenta is delivered.
Measured: 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.
This will measure how many women required to go to theatre as an emergency before the 15 minute trial has been completed.
Measured: From time of randomisation and administration of the study treatment to delivery of placenta (up to approximately 2 hours).
Systolic and diastolic blood pressure.
Fall in systolic or diastolic blood pressure of more than 15mmHg and/or increase in pulse of more than 20 beats/minute between baseline and 5 and 15 minutes postadministration of active/placebo treatment.
Measured: Study treatment to 15 minutes postadministration.
Need for blood transfusion
How many women will be required to have a blood transfusion between time of delivery and hospital discharge.
Measured: From the time of delivery of the placenta to time of discharge from hospital (up to 7 days).
Need for general anaesthesia
Will measure how many women required a general anaesthetic from when the study drug was administered until the placenta was delivered.
Measured: From time of randomisation and administration of the study treatment to delivery of placenta (up to approximately 2 hours).
Maternal Pyrexia
One or more temperature reading of more than 38°C.
Measured: Within 72 hours of delivery or discharge from hospital if discharge occurs sooner
Sustained uterine relaxation.
Sustained uterine relaxation after removal of placenta requiring uterotonics.
Measured: Within 24 hours of the time of delivery of the placenta.
Mean costs for each treatment allocation group
The mean costs will be summarised by treatment allocation group, and the incremental cost (cost saving) associated with the use of GTN will be estimated using an appropriately specified general linear model. The cost data will be presented alongside the primary and secondary outcome data in a cost-consequence balance sheet, indicating which strategy each outcome favours.
Measured: 6 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2014 (estimated)
- Study startSep 2014
- Primary completion26 Jul 2017
- Study completion5 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Placenta, RetainedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 1,107 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- University of Aberdeen, NHS Lothian
- Responsible party
- Sponsor
- Investigators
- Fiona C Denison, Dr, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02085213
- Sponsor's protocol ID
- HTA 12/29/01
- Other IDs
- 2013-003810-42, 12/29/01, 13/NE/0339
- Acronym
- GOT-IT
- Status last verified
- May 2018
- First submitted
- 4 Mar 2014
- Last updated
- 21 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 31887169
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GOT-IT Trial: A Pragmatic Group Sequential Placebo Controlled Randomised Trial to Determine the Effectiveness of Glyceryl Trinitrate for Retained Placenta.
- ClinicalTrials.gov ID
- NCT02085213
- Acronym / sponsor ID
- GOT-IT / HTA 12/29/01
- Conditions
- Placenta, Retained
- Keywords
- Retained placenta, Manual Removal of Placenta, Glyceryl Trinitrate
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,107 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- University of Aberdeen, NHS Lothian
- Study start
- Sep 2014
- Primary completion
- 26 Jul 2017 (actual)
- Study completion
- 5 Oct 2017 (actual)
- First posted
- 12 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Glyceryl Trinitrate | Experimental | Drug: Glyceryl TrinitrateNitrolingual 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. |
| Placebo | Placebo comparator | Drug: Matched PlaceboMatched placebo formulation (except for active ingredient of Glyceryl Trinitrate) with matched packaging and labelling. |
Who may qualify
- Ages
- 16 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Glyceryl TrinitrateAlso: GTN | Drug | Glyceryl Trinitrate |
| Matched PlaceboAlso: Dummy treatmentMatched placebo | Drug | Placebo |
Primary outcome
Need for Manual Removal of Placenta
Time frame: From time of randomisation up to 15-minutes post administration of study treatment
Defined as the placenta remaining undelivered 15 minutes post study treatment and/or being required within 15 minutes of treatment due to safety concerns.
9 secondary outcomes
Fall in haemoglobin
Time frame: First postnatal day (approximately 24 hours since the birth).
Time from randomisation to delivery of placenta.
Time frame: 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.
Time frame: From time of randomisation and administration of the study treatment to delivery of placenta (up to approximately 2 hours).
Systolic and diastolic blood pressure.
Time frame: Study treatment to 15 minutes postadministration.
Need for blood transfusion
Time frame: From the time of delivery of the placenta to time of discharge from hospital (up to 7 days).
Need for general anaesthesia
Time frame: From time of randomisation and administration of the study treatment to delivery of placenta (up to approximately 2 hours).
Maternal Pyrexia
Time frame: Within 72 hours of delivery or discharge from hospital if discharge occurs sooner
Sustained uterine relaxation.
Time frame: Within 24 hours of the time of delivery of the placenta.
Mean costs for each treatment allocation group
Time frame: 6 weeks.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2018.
- Derived from this study: PubMed 31887169Denison 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fiona C Denison, Dr principal investigator
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Glyceryl Trinitrate in people with Placenta, Retained, run by University of Edinburgh at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Need for Manual Removal of Placenta (time frame: From time of randomisation up to 15-minutes post administration of study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02085213, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2018.