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Retrospective Study of Patients Who Were Treated With Fondaparinux Pre-, Peri- and/or Postpartum for Prophylaxis or Treatment of Venous Thromboembolism (FondaPPP)

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01004939
First received: October 1, 2009
Last updated: July 28, 2011
Last verified: July 2011
  Purpose

The objective of this retrospective study is to gather information about how fondaparinux is used pre-, peri- and/or postpartum for both the prophylaxis and treatment of venous thromboembolism (VTE) in order to fill an information gap concerning the off-label use of fondaparinux during pregnancy.


Condition Intervention
Thromboembolism
Venous Thromboembolism
Drug: fondaparinux

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Retrospektive Studie zu Patientinnen, Die pränatal, Perinatal Oder Postnatal Prophylaktisch Oder Therapeutisch Mit Fondaparinux Behandelt Wurden

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants Receiving Fondaparinux in the Indicated Therapy Intervals [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: No ]
    The prenatal interval is defined as the interval of time until 3 days before birth. The perinatal interval is defined as the interval of time from 2 days before birth to one day after birth. The postnatal interval is defined as the interval of time beginning 2 days after birth.

  • Number of Participants With the Indicated Reason for Change to Fondaparinux [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: No ]
    It was possible for a participant to have changed to fondaparinux for multiple reasons.

  • Number of Participants Administered the Indicated Dose of Fondaparinux Per Day [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: No ]
  • Duration of Fondaparinux Administration [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: No ]
  • Duration of Prenatal Fondaparinux Administration [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: No ]
    The prenatal interval is defined as the interval of time until 3 days before birth.

  • Duration of Postnatal Fondaparinux Administration [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: No ]
    The postnatal interval is defined as the interval of time beginning 2 days after birth.

  • Number of Participants for Whom Fondaparinux Administration Was Interrupted for Birth [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
  • Number of Hours Before Birth That the Last Fondaparinux Dose Was Administered [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
  • Number of Hours After Birth at Which Fondaparinux Administration Was Restarted [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
  • Number of Participants With the Indicated Reason for the End of Fondaparinux Administration [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    It is possible that a participant stopped receiving Fondaparinux for multiple reasons.

  • Number of Participants With the Indicated Outcome of Pregnancy by Type of Birth [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
  • Number of Participants With the Indicated Type of Conception/Fertilization [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
  • Number of Participants Who Delivered a Single Child Versus Twins [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
  • Mean Weight of Newborn [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
  • Mean Height of Newborn [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
  • Mean Head Circumference of Newborn [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
  • Mean APGAR Score at 1, 5, and 10 Minutes After Birth [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    APGAR is a test performed by a doctor, midwife, or nurse at 1 and 5 minutes after birth. The 1-minute score determines how well the baby tolerated the birthing process; the 5-minute score assesses how well the newborn is adapting to the new environment. The health care provider examines the baby's breathing effort, heart rate, muscle tone, reflexes, and skin color. Each category is scored with 0 (worst score), 1, or 2 (best score), depending on the observed condition. The rating is based on a total score of 1-10, with 10 suggesting the healthiest infant.

  • Number of Newborns Who Had a "Healthy" Postnatal Classification [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    A "healthy" documentation was based on the investigators' individual assessment.

  • Number of Newborns With Abnormalities [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    No formal definition for abnormalities was predetermined; documentation was based on the investigators' individual assessment.


Secondary Outcome Measures:
  • Number of Participants Hospitalized Because of Thromboembolic Treatment [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    Thromboembolic treatment is a defined as prophylaxis for an elevated thromboembolic risk or therapeutic treatment of acute thromboembolism.

  • Duration of All Hospitalizations Under UFH, LMWH, and Fondaparinux Administration [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
  • Duration of Hospitalizations Before, During, and After Fondaparinux Administration [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
  • Number of Participants With Complications Under UFH/LMWH Therapy [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    A complication is defined as any thromoemolism, bleeding, skin change, HIT, amputation, or other complication (as indicated by investigator).

  • Number of Participants With Thromboembolisms Under UFH/LMWH Therapy [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    Any sign of thromboembolism as indicated by investigator was measured.

  • Number of Participants With Bleedings Under UFH/LMWH Therapy [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    No formal definition for bleeding was predetermined; documentation was based on the investigators' individual assessment.

  • Number of Participants With Skin Changes Under UFH/LMWH Therapy [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    No formal definition for skin change was predetermined; documentation was based on the investigators' individual assessment.

  • Duration From Start of UFH/LMWH Therapy to Skin Change [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    No formal definition for skin change was predetermined; documentation was based on the investigators' individual assessment.

  • Number of Participants Who Exhibited Observed Skin Changes and Also Had Erythema Associated With the Skin Changes Under UFH/LMWH Therapy [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    Erythema is defined as inflammation of the skin, associated with reddening, and is a frequent side effect of heparins.

  • Number of Participants Who Exhibited Observed Skin Changes and Also Had Skin Necrosis Associated With the Skin Changes Under UFH/LMWH Therapy [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    Skin necrosis is defined as the dying off of skin area because of allergic reaction. Skin necrosis is a severe side effect of heparins.

  • Number of Participants With Heparin-induced Thrombocytopenia (HIT II) Under UFH/LMWH Therapy [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    HIT II is characterized as a sudden decrease of thrombocyte count because of allergic response on heparin/platelet factor 4 (PF-4) complexes and is a severe and potentially fatal side effect of heparins. Usually, HIT occurs between Day 5 and Day 14 of exposure to UFH or LMWH.

  • Duration From Start of UFH/LMWH Therapy to HIT [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
  • Number of Participants With and Without Complications Under Fondaparinux Therapy [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    A complication is defined as any thromoemolism, bleeding, skin change, HIT, amputation, death, or other complication (as indicated by investigator).

  • Number of Participants With Thromboembolisms Under Fondaparinux Therapy [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    Any sign of thromboembolism as indicated by investigator was measured.

  • Number of Participants With Bleedings Under Fondaparinux Therapy [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    No formal definition for bleeding was predetermined; documentation was based on the investigators' individual assessment.

  • Number of Participants With Skin Changes Under Fondaparinux Therapy [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    No formal definition for skin change was predetermined; documentation was based on the investigators' individual assessment.

  • Number of Participants With Heparin-induced Thrombocytopenia (HIT II) Under Fondaparinux Therapy [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    The participant with HIT II was pretreated with LMWH; however, the serious adverse event of HIT II was documented after the participant switched to Fondaparinux treatment.

  • Duration From Start of Fondaparinux Therapy to HIT [ Time Frame: 4 months (all cases occurred between 2004 and 2010) ] [ Designated as safety issue: Yes ]
    For the 1 participant who developed HIT after receiving Fondaparinux, the number of days from start of therapy to HIT is presented.


Enrollment: 120
Study Start Date: March 2010
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
fondaparinux prescribed subjects
fondaparinux prescribed subjets
Drug: fondaparinux
fondaparinux

Detailed Description:

During pregnancy there is a generally enhanced risk to develop venous thromboembolism (VTE). Although such events are rare they may lead to serious risks for the mothers´ and children´s health. Compared with non-pregnant women, pregnant women have an about five-fold risk to develop VTE.

Due to their characteristic spectrum of side effects and the generally long duration of exposure in pregnancy the preferred anticoagulants may produce potentially dangerous side effects, as bleedings, heparin-induced thrombocytopenia (HIT), allergic reactions, osteoporosis, or congenital anomalies.

Today, low-molecular weight heparins (LMWH) are the preferred agents for anticoagulation in pregnancy. Compared with unfractioned heparins (UFH) LMWHs have the advantages of a lower bleeding risk, a lower rate of allergic reactions and HIT, a more predictable response and a longer half-life that makes dosing more convenient (od or bid).

Still, there is a considerable proportion of pregnancies where heparin intolerance (allergic reactions or HIT) that make it inevitable to change to another anticoagulant.

On the one hand, fondaparinux has repeatedly been reported successful in the VTE prophylaxis of pregnancies where allergic reactions on heparins, or heparinoids, had occurred. Additionally, a considerable amount of oral reports have reached GSK about an additional number of successful cases in the past.

On the other hand, we have no systematic and overall view about how many pregnancies have already been treated for which reasons, and how successful they were. Due to an increase of certain risk factors, as obesity or the growing age of mothers at childbirth with the associated need for anticoagulation, we expect an increased number of cases where alternative anticoagulation to heparins may be needed.

There are a number of potential advantages of fondaparinux over heparins, such as a once daily application, no dose adjustment needed to body weight and no monitoring of thrombocytes, a lower potential for causing intolerance reactions and no risk for HIT.

The objective of this retrospective study is to gather information about how fondaparinux is used pre-, peri- and/or postpartum for both the prophylaxis and treatment of VTE in order to fill an information gap concerning the off-label use of fondaparinux during pregnancy.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Pregnant women who received a prophylaxis against venous thromboembolism because of an elevated thromboembolic risk and who were therefore treated in a haemostaseological centre.

Criteria

Inclusion Criteria:

  • Patients who were treated with fondaparinux pre-, peri- and/or postpartum for more than 7 days for VTE prophylaxis or treatment, especially those with a history of abortion, and/or stillbirth, VTE, severe fetal and maternal complications during pregnancy, severe inherited or acquired thrombophilias, long-term anticoagulation (e. g. patients with mechanical heart valves) and/or intolerance to heparins or heparinoids or heparin-induced thrombocytopenia (HIT)

Exclusion Criteria:

  • Patients who were treated with fondaparinux for less than 7 days
  • Patient who were treated with fondaparinux only postpartum
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01004939

Locations
Germany
GSK Investigational Site
Mannheim, Baden-Wuerttemberg, Germany, 68167
GSK Investigational Site
Frankfurt, Hessen, Germany, 60590
GSK Investigational Site
Duisburg, Nordrhein-Westfalen, Germany, 47051
GSK Investigational Site
Muenster, Nordrhein-Westfalen, Germany, 48143
GSK Investigational Site
Bonn, Rheinland-Pfalz, Germany, 53115
GSK Investigational Site
Leipzig, Sachsen, Germany, 04289
GSK Investigational Site
Berlin, Germany, 13353
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: E.D. Derilus; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01004939     History of Changes
Other Study ID Numbers: 112937
Study First Received: October 1, 2009
Results First Received: June 30, 2011
Last Updated: July 28, 2011
Health Authority: Germany: Bundesinstitut für Arzneimittel und Medizinprodukte

Keywords provided by GlaxoSmithKline:
prophylaxis
venous thromboembolism
postpartum
fondaparinux
pregnancy

Additional relevant MeSH terms:
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Cardiovascular Diseases
Embolism and Thrombosis
Thrombosis
Vascular Diseases
Fondaparinux
PENTA
Anticoagulants
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014