Plain English Summary
Not provided at time of registration
Trial website
Contact information
Type
Scientific
Primary contact
Dr Andrew Weeks
ORCID ID
Contact details
Department of Obstetrics and Gynaecology
Liverpool Women's Hospital
Crown Street
Liverpool
L8 7SS
United Kingdom
+44 (0)151 702 4240
aweeks@liv.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
LWH 0481
Study information
Scientific title
Acronym
RELEASE
Study hypothesis
The injection of oxytocin down the umbilical vein has been proposed as a treatment for retained placenta. It can be performed by midwives in health centres and needs only the drug and a syringe. Its efficacy has been tested in a number of randomised trials with varying results. A recent meta-analysis by the Cochrane collaboration suggests that it is of borderline efficacy. However, the previous trials have used a wide variety of oxytocin doses as well as a method of injection that has been shown to deliver little of the oxytocin to the placental bed. The results of a recent observational study suggests that with higher oxytocin doses delivered through a tube passed up the umbilical vein, high success rates can be obtained. The results of a pilot study of 10 women, suggests that a dose of 50 IU in 30 ml saline may be effective at delivering the placenta.
A multi-centre randomised trial of this new method of umbilical vein injection is proposed. It will involve 572 women of over 34 weeks gestation with retained placenta of at least 30 minutes duration. The study centres will initially be Mulago Hospital, Kampala, Liverpool Women's Hospital, Liverpool and the Jessop Wing, Sheffield. The trial will be double-blind and women with retained placenta who are not bleeding excessively will be randomised to receive either oxytocin (50 IU in 30 ml saline) or placebo. Women will be eligible for inclusion from 30 minutes post-delivery and the primary outcome measure will be the incidence of manual removal of placenta. Women will go for immediate manual removal if haemorrhage occurs or at 30 minutes following the oxytocin injection. A study involving 572 women will have 80% power to detect a 20% reduction in the relative risk of manual removal with 95% significance.
The hypothesis is that intra-umbilical injection of oxytocin reduces the incidence of manual removal compared with placebo in the treatment of retained placenta.
Please note that as of 14/09/2007 the details of this trial were updated by the Principal Investigator (see contact details). Most changes are noted with the date 14/09/2007. The following amendment has also been made:
Pakistan has been added to the list of countries of recruitment as of 14/09/2007
Ethics approval
1. Ethical approval was granted for the RELEASE trial on 24th June 2004 by the London Multi-Centre Research Ethics Committee (reference MREC/03/2/075).
2. Local ethical approval has also been granted by the Pakistan and Uganda institutions involved.
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Retained Placenta
Intervention
Either 50 IU oxytocin or sterile water in 25 ml saline injected into the umbilical vein.
Please note the previous anticipated end date of this trial was 31/12/2007 (see hypothesis for details of this update).
Intervention type
Drug
Phase
Not Applicable
Drug names
Oxytocin
Primary outcome measure
Manual removal of the placenta following randomisation
Secondary outcome measures
Drop in haemoglobin, measured blood loss, need for transfusion, need for surgery
Overall trial start date
01/12/2004
Overall trial end date
31/05/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. 600 women with retained placenta for over 30 minutes
2. Written informed consent
3. Estimated gestation at least 34 weeks (or birth weight of 2 kg if gestation unknown)
4. Umbilical cord is clamped and cut
5. In the UK participants should be over 18 years of age, or over 16 and Gillick competent
6. In Uganda participants should be over 18
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
600 (572 as of 14/09/2007)
Participant exclusion criteria
1. Vaginal bleeding or maternal haemodynamic instability (Pulse >100 bpm or systolic blood pressure <100 mmHg) necessitating immediate placental removal
2. Torn umbilical cord making catheterisation impossible
3. Completely physiological third stage management (no cord cutting or clamping, no prophylactic oxytocics, no cord traction or fundal pressure)
4. Stillborn baby
Recruitment start date
01/12/2004
Recruitment end date
31/05/2008
Locations
Countries of recruitment
Pakistan, Uganda, United Kingdom
Trial participating centre
Department of Obstetrics and Gynaecology
Liverpool
L8 7SS
United Kingdom
Sponsor information
Organisation
Liverpool Women's Hospital (UK)
Sponsor details
Crown Street
Liverpool
L8 7SS
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Research organisation
Funder name
WellBeing (UK) (ref: W1/03)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
United Nations Development Programme (UNDP)/United Nations Population Fund (UNFPA)/World Health Organization (WHO)/World Bank - Special Programme of Research, Development and Research Training in Human Reproduction (HRP) - Ugandan part of the trial (ref: A35026)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Higher Education Commission of Pakistan (Pakistan) - funding for the Pakistan arm of the trial (added 14/09/2007)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
1. 2006 protocol in http://www.ncbi.nlm.nih.gov/pubmed/16167963
2. 2006 experiences and lessons for gaining informed consent http://www.ncbi.nlm.nih.gov/pubmed/16689989
3. 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/20004013
Publication citations
-
Protocol
Weeks A, Mirembe F, Alfirevic Z, The Release Trial: a randomised controlled trial of umbilical vein oxytocin versus placebo for the treatment of retained placenta., BJOG, 2005, 112, 10, 1458, doi: 10.1111/j.1471-0528.2005.00681.x.
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Experiences and lessons for gaining informed consent
Vernon G, Alfirevic Z, Weeks A, Issues of informed consent for intrapartum trials: a suggested consent pathway from the experience of the Release trial [ISRCTN13204258]., Trials, 2006, 7, 13, doi: 10.1186/1745-6215-7-13.
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Results
Weeks AD, Alia G, Vernon G, Namayanja A, Gosakan R, Majeed T, Hart A, Jafri H, Nardin J, Carroli G, Fairlie F, Raashid Y, Mirembe F, Alfirevic Z, Umbilical vein oxytocin for the treatment of retained placenta (Release Study): a double-blind, randomised controlled trial., Lancet, 2010, 375, 9709, 141-147, doi: 10.1016/S0140-6736(09)61752-9.