Condition category
Pregnancy and Childbirth
Date applied
13/09/2004
Date assigned
01/10/2004
Last edited
18/12/2009
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.releasestudy.org

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 measures

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

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

http://www.lwh.org.uk/

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

Results - basic reporting

Publication summary

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

  1. 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.

  2. 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.

  3. 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.

Additional files

Editorial Notes