ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12608000434392

Ethics application status

Approved

Date submitted

8/08/2008

Date registered

29/08/2008

Date last updated

4/12/2015

Type of registration

Prospectively registered

Titles & IDs

Public title

ACTIVE MANAGEMENT OF THE THIRD STAGE OF LABOUR WITHOUT CONTROLLED CORD TRACTION FOR PREVENTING POSTPARTUM HAEMORRHAGE: A RANDOMIZED NON-INFERIORITY CONTROLLED TRIAL

Scientific title

ACTIVE MANAGEMENT OF THE THIRD STAGE OF LABOUR WITHOUT CONTROLLED CORD TRACTION FOR PREVENTING POSTPARTUM HAEMORRHAGE: A RANDOMIZED NON-INFERIORITY CONTROLLED TRIAL

Secondary ID [1]

WHO A65554

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Postpartum haemorrhage

Condition category

Condition code

Reproductive Health and Childbirth

Normal pregnancy

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

uterotonic (oxytocin 10 IU IM) injection after delivery of the baby, cord clamping and cutting at approximately 3 minutes after birth.

Intervention code [1]

Prevention

Comparator / control treatment

uterotonic injection (oxytocin 10 IU IM), controlled cord traction following observation of uterine contraction and cord clamping and cutting at approximately 3 minutes after birth

Control group

Active

Outcomes

Primary outcome [1]

blood loss of 1000 ml or more at one hour and up to two hours for women who continue to bleed after one hour

Timepoint [1]

one hour and up to two hours for women who continue to bleed after one hour

Secondary outcome [1]

blood transfusion done

Timepoint [1]

until discharge

Secondary outcome [2]

use of additional uterotonics

Timepoint [2]

immediate postpartum period (24 hours)

Eligibility

Key inclusion criteria

pregnant women deliverying vaginally

Minimum age

15 Years

Maximum age

49 Years

Sex

Females

Can healthy volunteers participate?

Yes

Key exclusion criteria

1. Advanced first stage of labour (> 6 cm cervical dilatation)
2. Women who are too distressed to give consent regardless of cervical dilatation or phase of labour. Such evaluation will be made by the clinician in charge of the care of the woman.
3. Minors without a guardian
4. Planned caesarean section
5. If the birth is considered an abortion according to local limits
6. Women with twins or higher order multiple gestations
7. Women who are not capable of giving consent due to other health problems such as obstetric emergencies (e.g. eclampsia) or mental disorder.

Study design

Purpose of the study

Prevention

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Allocation of the random generated sequence will be by consecutively numbered envelopes. Allocation concealment will be achieved by using sealed opaque envelopes. Allocation will take place during second stage when vaginal delivery is imminent. Once the envelope is opened the name of the woman will be entered on the log file with the envelope number and that woman is enrolled in the trial.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

The random allocation sequence will be generated centrally at WHO Headquarters using computer generated random numbers. Randomization will be to two groups and stratified by country. Blocking with randomly varying groups of 6-8 will be used to restrict randomization within the strata.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

1/01/2009

Actual

1/06/2009

Date of last participant enrolment

Anticipated

Actual

30/10/2010

Date of last data collection

Anticipated

Actual

Sample size

Target

25000

Accrual to date

Final

24390

Recruitment outside Australia

Country [1]

Egypt

State/province [1]

Assiut

Country [2]

South Africa

State/province [2]

East London

Country [3]

Thailand

State/province [3]

Khon Kaen

Country [4]

Uganda

State/province [4]

Nsambya

Country [5]

Philippines

State/province [5]

Manila

Country [6]

Kenya

State/province [6]

Nairobi

Country [7]

India

State/province [7]

Belgaum

Country [8]

Argentina

State/province [8]

Rosario

Funding & Sponsors

Funding source category [1]

Other

Name [1]

United States Agency for International Development

Address [1]

Ronald Reagan Building
Washington, D.C. 20523-1000

Country [1]

United States of America

Primary sponsor type

Other

Name

World Health Organization

Address

Avenue Appia 20 - 1211 Geneva

Country

Switzerland

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

WHO Ethics Review Committee

Ethics committee address [1]

Avenue Appia 20 - 1211 Geneva

Ethics committee country [1]

Switzerland

Date submitted for ethics approval [1]

Approval date [1]

05/06/2008

Ethics approval number [1]

Summary

Brief summary

Background: The third stage of labour refers to the period between birth of the baby and complete expulsion of the placenta. Some degree of blood loss occurs after the birth of the baby due to separation of the placenta. This period is a risky period because uterus may not contract well after birth and heavy blood loss can endanger the life of the mother. Active management of the third stage of labour (AMTSL) reduces the occurrence of severe postpartum haemorrhage by approximately 60-70%. Active management consists of several interventions packaged together and the relative contribution of each of the components is unknown. Controlled cord traction is one of those components that require training in manual skill for it to be performed appropriately. If it is possible to dispense with controlled cord traction without losing efficacy it would have major implications for effective management of the third stage of labour at peripheral levels of health care.
Objective: The primary objective is to determine whether the simplified package of oxytocin 10 IU IM/IV is not less effective than the full AMTSL package.
Methods: A hospital-based, multicentre, individually randomized controlled trial is proposed. The hypothesis tested will be a non-inferiority hypothesis. The aim will be to determine whether the simplified package without CCT, with the advantage of not requiring training to acquire the manual skill to perform this task, is not less effective than the full AMTSL package with regard to reducing blood loss in the third stage of labour. 
The simplified package will include uterotonic (oxytocin 10IU IM) injection after delivery of the baby and cord clamping and cutting at approximately 3 minutes after birth. The full package will include the uterotonic injection (oxytocin 10 IU IM), controlled cord traction following observation of uterine contraction and cord clamping and cutting at approximately 3 minutes after birth. The primary outcome measure is blood loss of 1000 ml or more at one hour and up to two hours for women who continue to bleed after one hour. The secondary outcomes are blood transfusion, the use of additional uterotonics and measure of severe morbidity and maternal death.
We aim to recruit 25,000 women delivering vaginally in health facilities in eight countries within a 12 month recruitment period.
Management: Overall trial management will be from HRP/RHR in Geneva. There will be eight centres located in Argentina, Egypt, India, Kenya, Philippines, South Africa, Thailand and Uganda. There will be an online data entry system managed from HRP/RHR. The trial protocol was developed following a technical consultation with international organizations and leading researchers in the field. 
Expected outcomes: The main objective of this trial is to investigate whether a simplified package of third stage management can be recommended without increasing the risk of PPH. By avoiding the need for a manual procedure that requires training, the third stage management can be implemented in a more widespread and cost-effective way around the world even at the most peripheral levels of the health care system. This trial forms part of the programme of work to reduce maternal deaths due to postpartum haemorrhage within the RHR department in collaboration with other research groups and organizations active in the field.

Trial website

Trial related presentations / publications

Gülmezoglu AM, Lumbiganon P, Landoulsi S, Widmer M, Abdel-Aleem H, Festin M, Carroli G, Qureshi Z, Souza JP, Bergel E, Piaggio G, Goudar SS, Yeh J, Armbruster D, Singata M, Pelaez-Crisologo C, Althabe F, Sekweyama P, Hofmeyr J, Stanton ME, Derman R, Elbourne D. Active management of the third stage of labour with and without controlled cord traction: a randomised, controlled, non-inferiority trial. Lancet. 2012 May 5;379(9827):1721-7.

Public notes

Contacts

Principal investigator

Name

Dr A. Metin Gülmezoglu

Address

20 Avenue Appia - 1211 Geneva - Switzerland

Country

Switzerland

Phone

+41227913417

Fax

[email protected]

Contact person for public queries

Name

Metin Gulmezoglu

Address

Avenue Appia 20

Country

Switzerland

Phone

0041227913417

Fax

0041227914171

[email protected]

Contact person for scientific queries

Name

Metin Gulmezoglu

Address

Avenue Appia 20

Country

Switzerland

Phone

0041227913417

Fax

0041227914171

[email protected]

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Active management of the third stage of labour with and without controlled cord traction: a randomised, controlled, non-inferiority trial.		https://dx.doi.org/10.1016/S0140-6736%2812%2960206-2
Embase	Active management of the third stage of labour with and without controlled cord traction: A randomised, controlled, non-inferiority trial.	2012	https://dx.doi.org/10.1016/S01406736%2812%2960206-2
Embase	Distribution of postpartum blood loss: Modeling, estimation and application to clinical trials.	2018	https://dx.doi.org/10.1186/s12978-018-0641-1

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically