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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] 675 0
WHO A65554
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Postpartum haemorrhage 3529 0
Condition category
Condition code
Reproductive Health and Childbirth 3681 3681 0 0
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] 3245 0
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] 4591 0
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] 4591 0
one hour and up to two hours for women who continue to bleed after one hour
Secondary outcome [1] 7750 0
blood transfusion done
Timepoint [1] 7750 0
until discharge
Secondary outcome [2] 7751 0
use of additional uterotonics
Timepoint [2] 7751 0
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] 1104 0
Egypt
State/province [1] 1104 0
Assiut
Country [2] 1105 0
South Africa
State/province [2] 1105 0
East London
Country [3] 1106 0
Thailand
State/province [3] 1106 0
Khon Kaen
Country [4] 1107 0
Uganda
State/province [4] 1107 0
Nsambya
Country [5] 1108 0
Philippines
State/province [5] 1108 0
Manila
Country [6] 1109 0
Kenya
State/province [6] 1109 0
Nairobi
Country [7] 1110 0
India
State/province [7] 1110 0
Belgaum
Country [8] 1111 0
Argentina
State/province [8] 1111 0
Rosario

Funding & Sponsors
Funding source category [1] 3711 0
Other
Name [1] 3711 0
United States Agency for International Development
Country [1] 3711 0
United States of America
Primary sponsor type
Other
Name
World Health Organization
Address
Avenue Appia 20 - 1211 Geneva
Country
Switzerland
Secondary sponsor category [1] 3328 0
None
Name [1] 3328 0
Address [1] 3328 0
Country [1] 3328 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5764 0
WHO Ethics Review Committee
Ethics committee address [1] 5764 0
Avenue Appia 20 - 1211 Geneva
Ethics committee country [1] 5764 0
Switzerland
Date submitted for ethics approval [1] 5764 0
Approval date [1] 5764 0
05/06/2008
Ethics approval number [1] 5764 0

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 28824 0
Dr A. Metin Gülmezoglu
Address 28824 0
20 Avenue Appia - 1211 Geneva - Switzerland
Country 28824 0
Switzerland
Phone 28824 0
+41227913417
Fax 28824 0
Email 28824 0
[email protected]
Contact person for public queries
Name 11981 0
Metin Gulmezoglu
Address 11981 0
Avenue Appia 20
Country 11981 0
Switzerland
Phone 11981 0
0041227913417
Fax 11981 0
0041227914171
Email 11981 0
[email protected]
Contact person for scientific queries
Name 2909 0
Metin Gulmezoglu
Address 2909 0
Avenue Appia 20
Country 2909 0
Switzerland
Phone 2909 0
0041227913417
Fax 2909 0
0041227914171
Email 2909 0
[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
SourceTitleYear of PublicationDOI
EmbaseActive 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
EmbaseActive management of the third stage of labour with and without controlled cord traction: A randomised, controlled, non-inferiority trial.2012https://dx.doi.org/10.1016/S01406736%2812%2960206-2
EmbaseDistribution of postpartum blood loss: Modeling, estimation and application to clinical trials.2018https://dx.doi.org/10.1186/s12978-018-0641-1
N.B. These documents automatically identified may not have been verified by the study sponsor.