HEMOLEVEN® Expanded Access Program Prevention of Surgical/Postpartum Hemorrhage Severe Inherited Factor XI Deficiency (EAP)

• ClinicalTrials.gov Identifier: NCT01701947
• Expanded Access Status: No longer available
• First Posted: October 5, 2012
• Last Update Posted: August 23, 2013
• Sponsor: Laboratoire français de Fractionnement et de Biotechnologies
• Information provided by (Responsible Party): Laboratoire français de Fractionnement et de Biotechnologies

Study Description

Brief Summary:

The objective of the Expanded Access Program is to provide HEMOLEVEN, a replacement coagulation factor XI, to patients with severe inherited factor XI deficiency where, in the opinion of the treating physician, the benefits of administering selectively the missing factor outweigh the potential risks associated with the administration of fresh-frozen plasma.

Condition or disease	Intervention/treatment
Wound; Rupture, Surgery, Cesarean Section; Postpartum Hemorrhage; Surgery	Biological: Hemoleven

Detailed Description:

Many patients are asymptomatic until hemostatically challenged by surgery or trauma; so, the diagnosis is often made in late childhood or early adulthood but always after full liver maturation (i.e. 6 months) as reported by Andrew et al.

Spontaneous bleeding is rare, except menorrhagia, and bleeding occurs mainly after surgery or injury. Bleeding is observed mainly in surgical sites with high fibrinolytic activity such as mouth, nose, or the genitourinary tract.

Pregnancy, labor and delivery can also be challenging for women with FXI deficiency. In 1999 a study published in the American Journal of Hematology revealed that FXI levels are inconsistent during pregnancy. The incidence of postpartum hemorrhage is increased in women with factor XI deficiency. The incidence is 16% for the primary postpartum hemorrhage in FXI patients, compared with 5% in the general population. Moreover, the incidence is 24% for the secondary postpartum hemorrhage in comparison with that in the general obstetric population (0.7%). The authors recommend that FXI levels be obtained during the initial visit and monitored during the woman's third trimester. For all of these reasons it is important for women who suspect they might have a FXI deficiency to be tested and diagnosed before pregnancy.

Severe factor XI deficiency is defined by levels of <0.20 IU/mL. Such individuals have a high probability of post-operative hemorrhage. Individuals with levels between 0.20 IU/mL and the lower limit of the normal range, generally 0.65-0.80 IU/mL, are generally classified as having partial or mild deficiency with a lower risk of post-operative bleeding. Partial deficiency is being increasingly recognized following pre-operative tests or as a result of family screening. Thus partial factor XI deficiency is often diagnosed in asymptomatic individuals, creating management dilemmas because of the unpredictability of the bleeding risk. To differentiate an isolated or combined bleeding disorder in a patient with factor XI deficiency, other causes of bleeding should be investigated and excluded (e.g. von Willebrand disease, platelet disorders).

Study Design

• Study Type: Expanded Access
• Official Title: HEMOLEVEN® Expanded Access Program for Prevention of Surgical and Postpartum Hemorrhage in Patients With Severe Inherited Factor XI Deficiency

Interventions

Intervention Details:

• Biological: Hemoleven
  Replacement therapy
  Other Name: Human Coagulation Factor XI

Eligibility Criteria

• Ages Eligible for Study: 6 Months and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All

Criteria

Inclusion Criteria:

1. Severe inherited factor XI deficiency (FXI:C < 0.20 IU/mL i.e. <20 %)
2. Patient older than 6 months old and weight at least 8 kg
3. Known personal bleeding history
4. Patient requiring FXI replacement therapy when oral antifibrinolytic agents alone or other means are ineffective or are contraindicated
5. Scheduled to undergo an elective surgical procedure (including caesarean section) for which the patient requires hemostasis prophylaxis, which in the case of caesarean section is due to a history of postpartum bleeding, OR vaginal delivery for which the patient requires hemostasis prophylaxis due to a history of postpartum hemorrhage
6. Patient/guardian provides signed and dated Informed Consent for 'HEMOLEVEN Expanded Access Program' prior to entry into the program

Exclusion Criteria:

1. Personal history of thromboembolic events
2. Underlying cardiopulmonary disease of NYHA Class III or greater
3. History of severe reaction to any component of HEMOLEVEN notably to heparin or to its derivatives,including LMWH. Past history of serious type II heparin-induced thrombocytopenia (HIT)
4. Presence of antibody to FXI in the past or currently
5. Presence of any other condition that could contraindicate treatment with factor XI concentrate or lead the Physician/Investigator to believe treatment would not be in the best interest of the patient
6. Positive, confirmed pregnancy test for patients undergoing elective surgery (not applicable for caesarean section and prevention in vaginal delivery)
7. Lactating woman.

Of the seven exclusion criteria, the first four are included as a precautionary safety measure; the fifth is included to avoid a lack of efficacy.

The two last criteria are included to minimize confounding influences on the evaluation of patient safety. Oral contraception is not mandatory as a pregnancy test is scheduled at inclusion visit and before surgery.

Contacts and Locations

Locations

United States, Tennessee

Vanderbilt University Medical Center - Hemostasis & Thrombosis Ctr

Nashville, Tennessee, United States, 37232-5505

Sponsors and Collaborators

Laboratoire français de Fractionnement et de Biotechnologies

Investigators

• Principal Investigator: Anne T Neff, MD; Vanderbilt University Medical Center

More Information

• Responsible Party: Laboratoire français de Fractionnement et de Biotechnologies
• ClinicalTrials.gov Identifier: NCT01701947
• Other Study ID Numbers: HM11-1102
• First Posted: October 5, 2012
• Last Update Posted: August 23, 2013
• Last Verified: August 2013

Keywords provided by Laboratoire français de Fractionnement et de Biotechnologies:

Factor XI deficiency; EAP; postpartum hemorrhage; surgery; delivery; Child birth

Additional relevant MeSH terms:

Postpartum Hemorrhage; Factor XI Deficiency; Hemorrhage; Rupture; Pathologic Processes; Wounds and Injuries; Obstetric Labor Complications; Pregnancy Complications; Puerperal Disorders; Uterine Hemorrhage; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn