Comparison of Low and Intermediate Dose Low-molecular-weight Heparin to Prevent Recurrent Venous Thromboembolism in Pregnancy (Highlow)

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Status and phase: Completed; Phase 4

Conditions: Pulmonary Embolism; Deep Venous Thrombosis

Treatments: Drug: Intermediate dose nadroparin; Drug: Low dose nadroparin; Drug: Low dose enoxaparin; Drug: Intermediate dose dalteparin; Drug: Low dose dalteparin; Drug: Intermediate dose enoxaparin; Drug: Fixed low dose tinzaparin; Drug: Intermediate dose tinzaparin

Study type: Interventional

Funder types: Other

Identifiers

NCT01828697

NTR3894 (Registry Identifier)

NL40326.018.12 (Other Identifier)

Highlow study

2012-001505-24 (EudraCT Number)

Details and patient eligibility

About

This is a randomized-controlled open-label trial comparing two different doses of low-molecular-weight heparin (LMWH) in pregnant patients with a history of previous venous thromboembolism (VTE). Both doses are recommended doses in the 2012 guidelines of the American College of Chest Physicians (ACCP), but it is not known which dose is more efficacious in preventing recurrent venous thromboembolism in pregnancy.

Patients enter the study and will be randomized as soon as a home test confirms pregnancy. LMWH will be administered until 6 weeks postpartum. Follow-up will continue until 3 months postpartum. Patients will be recruited by their treating physician, either an obstetrician or internist.

Enrollment: 1,110 patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age: 18 years or older, and;
• Pregnancy confirmed by urinary pregnancy test, and;
• Gestational age < 14 weeks, and;
• Previous objectively confirmed VTE, either unprovoked, in the presence of use of oral contraceptives or estrogen/progestagen use, or related to pregnancy or the postpartum period, or minor risk factors (e.g. long distance travel, minor trauma).

Exclusion criteria

• Previous VTE related to a major provoking risk factor (e.g. surgery, major trauma or plaster cast immobilisation in the 3 months prior to VTE) as the sole risk factor, or;
• Indication for treatment with therapeutic dose anticoagulant therapy (e.g. treatment of acute VTE; permanent use of therapeutic anticoagulants outside of pregnancy), or;
• Inability to provide informed consent, or;
• Any contraindication listed in the local labelling of LMWH.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

1,110 participants in 2 patient groups

Low dose LMWH

Active Comparator group

Description:

Fixed low dose low-molecular-weight heparin: * Fixed low dose nadroparin, or; * Fixed low dose enoxaparin, or; * Fixed low dose dalteparin, or; * Fixed low dose tinzaparin.

Treatment:

Drug: Fixed low dose tinzaparin

Drug: Low dose nadroparin

Drug: Low dose dalteparin

Drug: Low dose enoxaparin

Intermediate dose LMWH

Active Comparator group

Description:

Intermediate dose low-molecular-weight heparin. Dosing is weight-adjusted according to the protocol. * Intermediate dose nadroparin, or; * Intermediate dose enoxaparin, or; * Intermediate dose dalteparin, or; * Intermediate dose tinzaparin.

Treatment:

Drug: Intermediate dose tinzaparin

Drug: Intermediate dose enoxaparin

Drug: Intermediate dose dalteparin

Drug: Intermediate dose nadroparin