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Trials. 2015 May 7;16:208. doi: 10.1186/s13063-015-0719-9.

ALIFE2 study: low-molecular-weight heparin for women with recurrent miscarriage and inherited thrombophilia--study protocol for a randomized controlled trial.

Author information

1
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands. p.g.dejong@amc.uva.nl.
2
Division of Reproductive Health, Warwick Medical School, The University of Warwick, Clifford Bridge Road, Coventry, CV2 2DX, UK. S.Quenby@warwick.ac.uk.
3
Department of Obstetrics and Gynecology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands. K.W.M.Bloemenkamp@lumc.nl.
4
Division Woman, Mother and Child, Tergooiziekenhuis, Rijksstraatweg 1, 1261 AN, Blaricum, the Netherlands. BBraams-Lisman@tergooi.nl.
5
Department of Obstetrics and Gynecology, Jeroen Bosch Ziekenhuis, Henri Dunantstraat 1, 5223, GZ s-Hertogenbosch, the Netherlands. jpdbruin@gmail.com.
6
Department of Gynaecology, Birmingham Women's Hospital and School of Clinical and Experimental Medicine, University of Birmingham, Vincent Drive, Birmingham, B15 2TT, UK. a.coomarasamy@bham.ac.uk.
7
Division of Hematology, CHU Ste-Justine, University of Montreal, 3175 Cote Ste-Catherine, Montreal, H3T 1C5, , QC, Canada. michele.david@umontreal.ca.
8
Hematology - Medical Oncology Division, Department of Medicine, New York-Presbyterian Hospital/Weill Cornell Medical College, 1305 York Avenue 7th Floor Room 51, New York, NY, 10021, USA. mtd2002@med.cornell.edu.
9
Department of Obstetrics and Gynecology, Radboud University Medical Center, Geert Grooteplein-Zuid 10, 6525 GA, Nijmegen, the Netherlands. Olivier.vanderHeijden@radboudumc.nl.
10
Department of Obstetrics and Gynecology, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands. a.hoek@umcg.nl.
11
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands. b.a.hutten@amc.uva.nl.
12
Department of Hematology and Hemostasis, Universitair Ziekenhuis Brussel - Vrije Universiteit Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium. Kristin.Jochmans@uzbrussel.be.
13
Department of Obstetrics and Gynecology, Máxima Medical Center, De Run 4600, Postbus 7777, 5500MB, Veldhoven, the Netherlands. C.Koks@mmc.nl.
14
Department of Obstetrics and Gynecology, Isala Klinieken, Dokter van Heesweg 2, 8025 AB, Zwolle, the Netherlands. w.k.h.kuchenbecker@isala.nl.
15
The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, 5000, , SA, Australia. ben.mol@adelaide.edu.au.
16
Division Woman & Baby, University Medical Center Utrecht, Postbus 85090, 3508 AB, Utrecht, the Netherlands. H.Torrance@umcutrecht.nl.
17
Department of Gynecology and Obstetrics at Maastricht University Medical Centre, P Debyelaan 25, 6229 HX, Maastricht, the Netherlands. hcj.scheepers@mumc.nl.
18
Department of Obstetrics and Gynecology, University of Illinois College of Medicine, 820 S Wood Street, M/C 808, Chicago, IL, USA. msteph@uic.edu.
19
Department of Obstetrics & Gynecology, Onze Lieve Vrouwe Gasthuis, Oosterpark 9, 1091 AC, Amsterdam, the Netherlands. H.R.Verhoeve@olvg.nl.
20
Department of Obstetrics, Gynecology and Reproductive Medicine, Amphia Hospital, Langendijk 75, 4819EV, Breda, the Netherlands. jantienvisser@gmail.com.
21
Department of Obstetrics, Vrije Universiteit Medical Center, PO Box 7057, , 1007 MB, Amsterdam, the Netherlands. JIP.deVries@vumc.nl.
22
Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands. m.goddijn@amc.uva.nl.
23
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands. s.middeldorp@amc.uva.nl.

Abstract

BACKGROUND:

A large number of studies have shown an association between inherited thrombophilia and recurrent miscarriage. It has been hypothesized that anticoagulant therapy might reduce the number of miscarriages and stillbirth in these women. In the absence of randomized controlled trials evaluating the efficacy of anticoagulant therapy in women with inherited thrombophilia and recurrent miscarriage, a randomized trial with adequate power that addresses this question is needed. The objective of the ALIFE2 study is therefore to evaluate the efficacy of low-molecular-weight heparin (LMWH) in women with inherited thrombophilia and recurrent miscarriage, with live birth as the primary outcome.

METHODS/DESIGN:

Randomized study of LMWH plus standard pregnancy surveillance versus standard pregnancy surveillance alone.

STUDY POPULATION:

pregnant women of less than 7 weeks' gestation, and confirmed inherited thrombophilia with a history of 2 or more miscarriages or intra-uterine fetal deaths, or both.

SETTING:

multi-center study in centers from the Dutch Consortium of Fertility studies; centers outside the Netherlands are currently preparing to participate.

INTERVENTION:

LMWH enoxaparin 40 mg subcutaneously once daily started prior to 7 weeks gestational age plus standard pregnancy surveillance or standard pregnancy surveillance alone. Main study parameters/endpoints: the primary efficacy outcome is live birth. Secondary efficacy outcomes include adverse pregnancy outcomes, such as miscarriage, pre-eclampsia, syndrome of hemolysis, elevated liver enzymes and low platelets (HELLP syndrome), fetal growth restriction, placental abruption, premature delivery and congenital malformations. Safety outcomes include bleeding episodes, thrombocytopenia and skin reactions.

DISCUSSION:

After an initial period of slow recruitment, the recruitment rate for the study has increased. Improved awareness of the study and acknowledgement of the need for evidence are thought to be contributing to the improved recruitment rates. We aim to increase the number of recruiting centers in order to increase enrollment into the ALIFE2 study. The study website can be accessed via www.ALIFE2study.org.

TRIAL REGISTRATION:

The ALIFE2 study was registered on 19 March 2012 under registration number NTR3361.

PMID:
25947329
PMCID:
PMC4453290
DOI:
10.1186/s13063-015-0719-9
[Indexed for MEDLINE]
Free PMC Article

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