Prof Beverley Hunt, Guy’s & St Thomas’ NHS Foundation Trust

Kings College, London Medical Director of Thrombosis UK

Twitter: @bhwords

Tranexamic acid & post partum haemorrhage

Tranexamic acid a lysine binding analogue

TXA IN TRAUMATIC HAEMORRHAGE

• 20,211 trauma patients with or at risk of significant

haemorhage randomised to TXA or placebo.

• Results show a 15% relative reduction in death from

bleeding, and 9% from all cause mortality in the TXA

treated group.

• No evidence of an increase in adverse effects, including thromboembolic events, in the TXA treated group.

Rough guide to which groups benefit from TA worldwide

Number Preventable trauma worldwide

deaths with TA

Those presenting with massive

blood loss

20,000

Those presenting with bleeding

but not MBL

100,000

TOTAL 120,000

Systematic review identified 129 trials between 1972-2011 including 10 488

patients

Ker et al. BMJ 2012; 344:e3054

TXA

TXA better TXA worse

0.62 (0.58-0.65)

RR (95% CI)

0.4 0.8 1.2 1.6

Transfusion

TXA

RR (95% CI)

TXA better TXA worse

0 0.4 0.8 1.2 1.6

0.61 (0.38-0.98)

Mortality

72

trials 95 trials

TXA use in surgery

Protocol Code: ISRCTN11225767

Tranexamic acid for the treatment of gastrointestinal

bleeding: an international randomised,

double blind placebo controlled trial

Topical use of tranexamic acid S. Alshryda et al, North Tees & Hartlepool Hosp, J Bone Joint Surg Am, 2013 Nov 06;95(21):1961-1968. of of

The TRANX-K (Tranexamic Acid in Total Knee Replacement) trial was a double-blind, placebo-controlled trial of the effect of topical (intra-articular) application of TA on blood loss & transfusion following a unilateral total knee replacement.

1gm TA in 50mls saline sprayed into the wound at the end of TKR

TA reduced

-blood transfusion by 15.4% blood loss by 168 mL the length of stay by 1.2 days

New patent: self-propelled particles that transport cargo through

flowing blood and halt hemorrhage.

R. Baylis et al. Science Advances, 2015; 1 (9): e1500379 DOI:

THE WOMAN TRIAL OVERVIEW AND PROGRESS

Protocol Code: ISRCTN76912190

MATERNAL MORTALITY • 355,000 (99%) of deaths occurred in

developing countries.

• The range of uncertainty plausibly is as low as

265,000 or as high as 503,000.

• The maternal mortality ratio highest in developing countries – 290 in developed

regions.

WHO, UNICEF, UNFPA and The World Bank (2010). Trends in Maternal Mortality: 1990 to 2008

An estimated 358,000 maternal deaths occurred worldwide in 2008

• Three randomised trials with 461 participants.

• In two trials, TXA was administered before the incision for a

caesarean section.

• In one trial, TXA was administered immediately after

spontaneous vaginal delivery.

SYSTEMATIC REVIEW OF TXA IN PPH

SYSTEMATIC REVIEW OF TXA IN PPH REDUCED BLOOD LOSS

but trials quality too poor to confirm or refute moderate

effects.

TXA better TXA worse

-200 -100 100 200 0

Study

Gai 2004

Gohel 2007

Yang 2001

Total (95% CI)

RATIONALE FOR THE WOMAN TRIAL • Bleeding is a leading cause of postpartum mortality.

• Blood transfusion can be dangerous.

• Antifibrinolytics reduce blood loss after surgery.

• CRASH-2 trial of 20,211 trauma patients showed TXA safely reduces the risk of death from bleeding by a relative 15%.

• Trials in PPH too small to confirm or refute moderate effects.

• A simple, relatively cheap intervention like TXA could prevent deaths and morbidity associated with PPH.

AIMS • Primary outcomes: To quantify the effect of

tranexamic acid (TXA) on death and hysterectomy in women with clinician diagnosed PPH.

• Secondary outcomes to quantify the effect of TXA on:

• Death

• Surgical Interventions

• Blood transfusion

• Health status measured using the EQ-5D scale

• Thromboembolic events

• Other relevant medical events

• Length of stay at hospital/time spent in an intensive care unit

• Receipt of mechanical ventilation

• Status of breastfed baby/ies

CONTRIBUTIONS

0.1%

0.2%

0.3%

0.4%

0.9%

1.7%

1.9%

2.0%

2.4%

2.7%

3.0%

3.3%

3.6%

4.5%

5.2%

5.2%

10.5%

20.6%

31.6%

0% 5% 10% 15% 20% 25% 30% 35%

Colombia

Egypt

Ghana

Jamaica

Burkina Faso

Ethiopia

Bangladesh

Zambia

Democratic Republic of Congo

Tanzania

Albania

Nepal

United Kingdom

Sudan

Kenya

Cameroon

Uganda

Pakistan

Nigeria

Percentage Contribution

TRIAL SUMMARY STATISTICS

Fre

qu

en

cy p

er

Ag

e

Ra

ng

e

0

200

400

600

800

1000

1200

1400

1600

1800

15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 53 55 56

Age

0

10

20

30

40

50

60

70

80

90

100

Vaginal Caesarean section

TYPE OF DELIVERY

TYPE OF DELIVERY

64%

Other

Placenta praevia/accreta

Surgical trauma/tears

Unknown

Uterine atony

Percentages

CAUSE OF DEATH

Bleeding 69

Pulmonary embolism 4

Other 27

Percentages

EVENT RATES

The primary outcomes for the WOMAN TRIAL are:

1. Death 2. Hysterectomy

Numbers for the Trial

Women who died 373

Women with hysterectomy 750

Total events 1004

Total event rate = [Death] + [Hysterectomy] – [Woman who had a hysterectomy then died]

0%

1%

2%

3%

4%

5%

6%

7%

Women who died Women with

hysterectomy

Total Events

% Trial

BLOOD LOSS DISTRIBUTION

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

Blood Loss in m/l

Nu

mb

er

of

Pa

tie

nts

PROGRESS SUMMARY • The trial is completed with 20,000 women recruited from 202 sites in 20 countries.

• 88% women gave birth at the recruiting hospital.

• 96% received prophylactic uterotonics.

• Primary causes of PPH were:

• Uterine atony in 65% • Surgical/ trauma/tears in 19% • Placenta previa/accretes in 10% • Other causes 7% • Unknown cause 1%

• 2% died and 5% had a hysterectomy.

• Of those who had a hysterectomy, 0.8% died.

• The majority (71%) who died, delivered in the randomising hospital.

CONCLUSIONS

• Women continue to die from PPH

even when they deliver in hospital.

• More effective treatments are

needed to improve outcomes.

• The WOMAN trial will resolve the uncertainty regarding the

effectiveness and safety of TXA as

a treatment for PPH.

Make sure you know the result by registering

your interest at

www.womantrial.LSHTM.ac.uk

Clinical Trials Unit London School of Hygiene & Tropical Medicine

Keppel Street, London WC1E 7HT

Tel: +44(0)20 7299 4684 Fax: +44(0)20 7299 4663

Email: thewomantrial@LSHTM.ac.uk

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