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Nuwiq Dosing and Outcomes In the ManagEment of Women/Girls With Haemophilia A Needing FVIII Treatment for Surgery

Phase 4
Recruiting
Conditions
Hemophilia A
Interventions
Registration Number
NCT05936580
Lead Sponsor
Octapharma
Brief Summary

Recombinant factor VIII for the prevention of bleeding in women/girls with haemophilia A undergoing major surgery

Detailed Description

Female patients with mild to moderate haemophilia A will often need FVIII concentrates to provide haemostatic cover during major surgery. This prospective, open-label, non-controlled, single-arm, multinational, multicentre study aims to evaluate the overall perioperative haemostatic efficacy of Nuwiq in women/girls over 12 with haemophilia A undergoing major surgery requiring FVIII treatment

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
28
Inclusion Criteria
  1. Women/girls with haemophilia A (FVIII:C ≥1-<40%) according to medical history
  2. At least 12 years of age
  3. Scheduled to undergo major elective surgery requiring FVIII treatment
  4. Freely given written informed consent of the patient, or parent/legal representative where applicable, obtained in accordance with local regulations
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Exclusion Criteria
  1. Coagulation disorder other than haemophilia A
  2. Present or past FVIII inhibitor (≥0.6 Bethesda units [BU]/mL)
  3. Severe liver or kidney disease (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST] levels >5 times the upper limit of normal; or creatinine >120 μmol/L)
  4. Known hypersensitivity to Nuwiq's active substance or its excipients (sucrose, sodium chloride, calcium chloride dihydrate, arginine hydrochloride, sodium citrate dihydrate, poloxamer 188)
  5. Pregnancy
  6. Already had surgery in this study
  7. Current participation in another interventional clinical trial
  8. Treatment with any investigational medicinal product (IMP) within 30 days prior to screening visit
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
NuwiqNuwiqAll patients receiving Nuwiq (recombinant FVIII). Nuwiq will be administered intravenously in accordance with the relevant prescribing information. Treatment will be repeated as necessary every 8-24 hours until adequate wound healing, then - if required - for at least another 7 days to maintain FVIII plasma levels of 30-60 IU/dL.
Primary Outcome Measures
NameTimeMethod
Overall haemostatic efficacyDuring surgery and until completion of wound healing (e.g. removal of sutures, cessation of drainage, etc.) as defined by the investigator, during the study duration of 30 ± 3 days after the day of surgical procedure

Overall haemostatic efficacy of treatment measured as binary "success" or "failure". The overall perioperative haemostatic efficacy of Nuwiq will be adjudicated by an Independent Data Monitoring Committee (IDMC) and determined using a composite assessment algorithm that considers the surgeon's assessment of intraoperative haemostatic efficacy and the investigator's assessment of postoperative haemostatic efficacy to classify the overall haemostatic efficacy as success or failure.

Secondary Outcome Measures
NameTimeMethod
FVIII inhibitor formationFrom start of first Nuwiq injection to 30 ±3 days following the surgical procedure

Incidence of FVIII inhibitor formation

Intraoperative haemostatic efficacyDuring surgery: From first skin incision to last suture

Assessment of intraoperative haemostatic efficacy of Nuwiq using a 4-point ordinal scale:

Excellent: Intraoperative blood loss was lower than or equal to the average expected blood loss for the type of procedure performed in a patient with normal haemostasis and of the same sex, age, and stature

Good: Intraoperative blood loss was higher than the average expected blood loss but lower or equal to the maximal expected blood loss for the type of procedure in a patient with normal haemostasis.

Moderate: Intraoperative blood loss was higher than the maximum expected blood loss for the type of procedure performed in a patient with normal haemostasis, but haemostasis was controlled.

None: Haemostasis was uncontrolled, necessitating a change in the clotting factor replacement regimen.

Postoperative haemostatic efficacyDuring surgery and until completion of wound healing (e.g. removal of sutures, cessation of drainage, etc.) as defined by the investigator, during the study duration of 30 ± 3 days after the day of surgical procedure

Assessment of postoperative haemostatic efficacy of Nuwiq using a 4-point ordinal scale:

Excellent: No postoperative bleeding or oozing that was not due to complications of surgery. All postoperative bleeding (due to complications of surgery) was controlled with Nuwiq as anticipated for the type of procedure.

Good: No postoperative bleeding or oozing that was not due to complications of surgery. Control of postoperative bleeding due to complications of surgery required increased dosing with Nuwiq or additional injections not originally anticipated for the type of procedure.

Moderate: Some postoperative bleeding and oozing that was not due to complications of surgery. Control of postoperative bleeding required increased dosing with Nuwiq or additional injections not originally anticipated for the type of procedure.

None: Extensive uncontrolled postoperative bleeding and oozing.

Allogenic blood productsDuring surgery and until completion of wound healing (e.g. removal of sutures, cessation of drainage, etc.) as defined by the investigator, during the study duration of 30 ± 3 days after the day of surgical procedure

Use of allogeneic blood products (red blood cells, platelets, and other blood products)

FVIII plasma levels≤30 minutes before and 15-30 minutes after Nuwiq injection

Perioperative plasma levels

Perioperative haemostatic efficacy per WFH criteria≤30 minutes before and 15-30 minutes after Nuwiq injection

Assessed using 4-point scale recommended by WFH:

Excellent: Intra- and post-operative blood loss similar to non-haemophilic patient. No extra doses of FVIII/bypassing agents needed Good: Intra- and/or post-operative blood loss slightly increased over expectation for non-haemophilic patient, but judged to be clinically insignificant. No extra doses of FVIII/bypassing agents needed Fair: Intra- and/or post-operative blood loss increased over expectation for the non-haemophilic patient, and additional treatment needed. Extra dose of FVIII/bypassing agents needed, or increased blood component of anticipated transfusion requirement Poor: Significant intra- and/or post-operative blood loss substantially increased over expectation for non-haemophilic patient, requires intervention not explained by medical issue other than haemophilia. Unexpected hypotension, unexpected transfer to ICU due to bleeding, substantially increased blood component of the anticipated transfusion requirement

Adverse eventsFrom start of first Nuwiq injection to 30 ±3 days following the surgical procedure

Incidence of adverse events recorded during the full study period

Thrombotic eventsFrom start of first Nuwiq injection to 30 ±3 days following the surgical procedure

Incidence of thrombotic events during the study

Trial Locations

Locations (13)

UT Health San Antonio

🇺🇸

San Antonio, Texas, United States

Gerinnungszentrum Rhein-Ruhr

🇩🇪

Duisburg, Germany

St. James's University Hospital

🇬🇧

Leeds, United Kingdom

Helsinki University Hospital,Coagulation Disorder Unit

🇫🇮

Helsinki, Finland

Avenue de la République

🇫🇷

Chambray-lès-Tours, France

CHU de Nantes Hôtel-Dieu

🇫🇷

Nantes, France

Universitätsklinikum Bonn,Institut für Experimentelle Haematologie und Transfusionsmedizin

🇩🇪

Bonn, Germany

Universitätsklinikum Hamburg Eppendorf,II. Medizinische Klinik und Poliklinik

🇩🇪

Hamburg, Germany

Aziendo Ospedaliera "Puglieze Ciaccio"

🇮🇹

Catanzaro, Italy

Policlinico "P. Giaconne"

🇮🇹

Palermo, Italy

Clinical Center for Serbia

🇷🇸

Belgrade, Serbia

Hospital Universitario la Paz

🇪🇸

Madrid, Spain

Hospital Universitario Virgen del Rocio

🇪🇸

Sevilla, Spain

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