Low Weight Heparin prOphylaxis for Placental-Mediated Complications of PrEgnancy (HOPPE)

Enoxaparin for the Prevention of Placental-Mediated Complications of Pregnancy in Women With Obstetric History or Abnormal Uterine Artery Doppler at First Trimester Ultrasound and Without Thrombophilia: a Multicenter Randomized Controlled Trial

This is a Multicenter, randomized, open-label, parallel groups study to test the hypothesis that prophylactic low molecular weight heparin (LMWH) (enoxaparin) initiated before 14 weeks of gestation could improve maternal and perinatal outcome in women at high risk for developing placental-mediated pregnancy complications.

Study Overview

• Status: Completed
• Conditions: Preeclampsia; Placental Insufficiency; High Risk Pregnant Women
• Intervention / Treatment: Drug: Enoxaparin

• Study Type: Interventional
• Enrollment (Anticipated): 361
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain, 08950
      • Hospital Sant Joan de Déu
    • Sant Boi de Llobregat, Barcelona, Spain, 08830
      • Parc Sanitari Sant Joan de Deu
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
      • Hospital de Cruces

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pregnant women ≥18 years
• Gestational age < 14 weeks at randomisation

• One or more of the following complications in a previous pregnancy:

  • Severe PE resulting in delivery before 32 weeks of gestation
  • Newborn weight less than the 10th percentile and documented abnormal Doppler in the umbilical artery during pregnancy before 32 weeks gestation
  • Abruption of placenta
  • Unexplained intrauterine death between 20-41,6 weeks of gestation secondary of placental insufficiency or
• Uterine arteries Pulsatility Index (mPI) Doppler ≥95th percentile at 11-14 weeks of gestation.

Exclusion Criteria:

• Multiple pregnancy
• Abnormal thrombophilia study
• Alcohol or illicit drug use
• Severe fetal malformations or chromosomal abnormalities
• Previous history of infertility ( 3 or more early miscarriages)
• Maternal HIV, Cytomegalovirus or toxoplasma infection
• Known fetal abnormality or chromosomal defect at randomisation
• Women with previous venous or arterial thrombotic event
• Organic lesions that could increase the hemorrhagic risk: gastric ulcus, stroke, a recent hemorrhagic event, high risk situations for hemorrhagic event
• Known allergy to heparin or LMWH, thrombopenia or thrombosis episode due to heparin treatment
• Contraindication to LMWH
• An absolute indication for anticoagulant therapy: venous deep thrombosis, pulmonary embolism, ovaric hyperestimulation, cardiophaty, others
• Metabolic disorders a risk for development of PE and/or IUGR: Type I diabetes, hipertiroidism, chronic renal insufficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enoxaparin; Subcutaneous administration of one dose daily of enoxaparin	Drug: Enoxaparin; 40 mg (4000 IU) women <80 kg at the time of randomization or 60 mg (6000 IU) women> 80 kg at the time of randomization One dose daily. Subcutaneous administration. Treatment periods: the same day of the Initiation visit (from 9 to 13.6 weeks of gestation) until 36 weeks gestation.
No Intervention: expectant management; Usual management

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of any of these complications of placental insufficiency	Development of any of these complications of placental insufficiency: preeclampsia, intrauterine growth restriction, abruption placentae, and/or intrauterine fetal demise	from date of randomization until the date of delivery (assessed up to 30 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gestational age at birth	Gestational age at birth	from date of randomization until the date of delivery (assessed up to 30 weeks)
Days of hospitalization during pregnancy	Days of hospitalization during pregnancy	from randomization to the time of delivery (30 weeks)
Days of maternal hospitalization in the postpartum period	Days of maternal hospitalization in the postpartum period	from delivery until discharge (an expected average of one week)
Neonatal Data	weight, height, head circumference, Apgar score 1-5 min, arterial pH, venous base excess (BE) of umbilical cord gases, and complications	after the delivery (an expected average of one month)

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute
• Collaborators: Parc Sanitari Sant Joan de Déu; Hospital Vall d'Hebron; Hospital Sant Joan de Deu; Hospital de Cruces
• Investigators: Study Chair: Lluís Cabero, MD PhD, Hospital Vall d'Hebron; Principal Investigator: Elisa Llurba, MD, Hospital Vall d'Hebron; Principal Investigator: Maria Dolores Gómez, MD, Hospital Sant Joan de Déu; Principal Investigator: Txantón Martínez-Astorquiza, MD, Hospital de Cruces; Principal Investigator: Raul De Diego, M.D., Parc Sanitari Sant Joan de Deu

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: June 28, 2011
• First Submitted That Met QC Criteria: July 4, 2011
• First Posted (Estimate): July 6, 2011

Study Record Updates

• Last Update Posted (Estimate): December 21, 2016
• Last Update Submitted That Met QC Criteria: December 20, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Pregnancy; Preeclampsia; Placental insufficiency
• Additional Relevant MeSH Terms: Placenta Diseases; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Pregnancy Complications; Placental Insufficiency; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin
• Other Study ID Numbers: HOPPE-Trial; 2010-023597-39 (EudraCT Number)