1. ALIFE2 Study Call for participation
Paulien de Jong
Dr. Mariëtte Goddijn
Prof. dr. Saskia Middeldorp

2. Disclosures Paulien de Jong
Research contracts: -
Consulting:
Employment in industry:
Stockholder of a healthcare company:
Owner of a healthcare company:
Other:

3. Rationale for the study
Inherited thrombophilia is associated with pregnancy loss1,2
recurrent early loss: OR 1.9 – 2.72
Thrombosis of (micro-)vasculature of placenta
Inhibition of throphoblast differentiation and subsequent placentation3
Possible therapy for pregnancy loss: anticoagulants ?
1. Rey, Lancet, 2003
2. Robertson, Br. J. of Haematology 2006
3. Quenby, Fertility and Sterility, 2005

4. ALIFE study 364 women Randomized 123 aspirin and nadroparin
121 placebo
Live birth:
69%
Live birth:
62%
Live birth:
67%
RR 1.03
RR 0.92
Reference
RR 1.31
RR 1.22
Reference
Inherited
thrombophilia
Kaandorp NEJM 2010

5. ALIFE2 study Objective:
to evaluate the efficacy of LMWH in women with recurrent miscarriage and inherited thrombophilia
Primary outcome:
live birth
Secondary outcomes:
adverse pregnancy outcomes & safety
Design:
Multicenter, investigator-initiated study
Open label

6. In-/exclusion criteria
Inclusion criteria:
≥2 miscarriages and / or IUFDs
Age 18-42
Confirmed inherited thrombophilia:
Factor V Leiden mutation, prothrombin gene mutation, protein C deficiency, protein S deficiency, antithrombin deficiency
Exclusion criteria:
Pregnancy duration ≥ 7 weeks
Indication for anticoagulant treatment during pregnancy (for instance prosthetic heart valves, a history of venous thromboembolism or antiphospholipid syndrome)
Contraindications to LMWH (previous heparin induced thrombocytopenia, active bleeds or renal insufficiency with creatinine clearance of less than 30ml/min)
Known allergy to at least 3 different LMWH preparations
Previous inclusion in the ALIFE2 study (for another pregnancy)

7. In-/exclusion criteria
Inclusion criteria:
≥2 miscarriages and / or IUFDs
Age 18-42
Confirmed inherited thrombophilia:
Factor V Leiden mutation, prothrombin gene mutation, protein C deficiency, protein S deficiency, antithrombin deficiency
Exclusion criteria:
Pregancy duration ≥7 weeks
Indication for anticoagulant treatment during pregnancy (for instance prosthetic heart valves, a history of venous thromboembolism or antiphospholipid syndrome)
Contraindications to LMWH (previous heparin induced thrombocytopenia, active bleeds or renal insufficiency with creatinine clearance of less than 30ml/min)
Known allergy to at least 3 different LMWH preparations
Previous inclusion in the ALIFE2 study (for another pregnancy)

8. ® Primary efficacy outcome: Live birth M M
Confirmed Inherited thrombophilia
LMWH +
standard pregnancy surveillance
Recruitment
delivery
Follow-up
M M
Positive urine pregnancy test
≥ 2 miscarriages and/or IUFDs
Standard pregnancy surveillance
6 weeks

9. Participating centers
- AMC - Amphia
- UMCG - Jeroen Bosch Ziekenhuis
- VUMC - Isala Klinieken
- MUMC - OLVG
- UMCN - Maxima MC
- UMCU
Foreign centers:
Brussels
USA/UK/Canada/Australia…..

10. Inclusions
n=399
Sample size
Inclusions
n=15

11. We are looking for you! Think of ALIFE2 in case of
Recurrent miscarriage and/or IUFD
Women with inherited thrombophilia
Refer study candidates
Contact us for questions regarding eligibility

12. www.ALIFE2study.org p.g.dejong@amc.uva.nl s.middeldorp@amc.uva.nl