Atenativ Effect on Uterine Blood Flow and Preeclampsia

Phase 4

Withdrawn

• Conditions: Antithrombin III Deficiency
• Interventions: Drug: Atenativ

• Registration Number: NCT02278575
• Lead Sponsor: Vastra Gotaland Region

Brief Summary

The study will be an open controlled pilot study of 6 patients with early-onset severe preeclampsia. Patients will receive Atenativ in addition to conventional therapy The patients will be followed up within the study until three days after delivery. Laboratory analyses and uterine and umbiliacal blood flow will be determined.

Detailed Description

The study will be an open controlled pilot study of 6 patients with early-onset severe preeclampsia. Patients will receive Atenativ in addition to conventional therapy The patients will be followed up within the study until three days after delivery. In addition to conventional therapy, i.v. administration of Atenativ will be given in a dosage aimed to raise the plasma level of AT initially to 120% (1.2 kIU/L) The goal is to achieve and maintain plasma activity of about 100% during two weeks. The dose of Atenativ is based on the actual plasma level of AT measured 2 hours before the dose. During the first two days of treatment plasma samples will be drawn for the measurement of AT activity twice a day, once before and 12 hours after infusion in order to monitor the dosage. Thereafter and until study discontinuation AT will be measured once a day. The treatment will continue for two weeks if plasma AT III is below 100% (1.0 kIU/L).Uterine blood flow is measured before, during and after the AT infusion. Demographic data, medical history and other background data (age, weight, height, gestational week, smoker or not, gravidity, parity, previous hypertension, previous medication etc) will be recorded in order to ensure that the inclusion criteria are met and to verify patient identity and inclusion status. The week of gestation when the patient is included in the study as well as the week of gestation at delivery is recorded.

The type of delivery (vaginal or caesarean section as well as planned or acute) will also be recorded.. General haemostatic parameters are to be analyzed before start of treatment and then every day during treatment and thereafter at least twice a week. Special haemostatic parameters are Placental growth factor, S-Flt-1, VEGF and Syndecan-1. They will be sampled before start of treatment and during treatment once a week. The samples will be collected and frozen and not analyzed before the termination of the study.

Study Timeline

• Study First Submitted: 2014-10-28
• Study First Submitted QC: 2014-10-29
• Study First Posted: 2014-10-30
• Study Start: 2016-01
• Primary Completion: 2017-05
• Study Completion: 2017-05
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-22
• Last Update Posted: 2017-09-26

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

1. Pregnant woman in gestational week 23+0 - 29+0

2. Severe preeclampsia as defined by international criteria (1,2)

   • Blood pressure >160/110 mmHg (measured twice 30 minutes apart). proteinuria (>5 .0 g/L per 24 hours or >3 + labstick in at least two random samples six hours apart) after 20th gestational week.
   • Blood pressure >140/90 mmHg and proteinuria >5.0 g/24 h.
   • preeclampsia ( blood pressure > 140/90 and proteinuria >0.3 g/24 h) with IUGR or subjective symptoms as epigastic pain (HELLP), headache, dizziness or visual disturbancies, oligouri < 600 ml/24 h, coagulation disturbancies.

3. AT level <0.8 kIE/L

Exclusion Criteria

1. History of congenital AT deficiency 2. Severe preeclampsia with demand on acute delivery within 24 hours according to the investigators judgments 3. Concomitant administration of anticoagulants and platelet inhibitors within 2 weeks 4. Chronic renal disease 5. Diabetes melittus or gestational diabetes 6. Intrauterine fetal death 7. Participation in another clinical study 8. Multiple pregnancies

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Consisting of treatment with Atenativ	Atenativ	During two weeks antithrombin concentrate(Atenativ) will be administered in order to maintain normal levels of antithrombin

Primary Outcome Measures

Name	Time	Method
Blood flow in uterin and umbilical artery	up to day 14

Secondary Outcome Measures

Name	Time	Method
fetal outcome	at birth	CTG, blood flow, Apgar score, birthweight
bleeding complications	during pregnancy and at delivery	measurements of bleeding before and after placenta delivery

Trial Locations

Locations (1)

Dept Obstetrics, Sahlgrenska University Hospital; 🇸🇪 Gothenburg, Sweden