Impact of Emicizumab on Activated Clotting Time Using the i-STAT Alinity Analyzer

NCT05856903 | Unknown

• 2 other identifiers: 38RC23.01242023-A00897-38
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Emicizumab (Hemlibra®) is a subcutaneous hemostatic treatment approved in 2019 for the prophylaxis in severe hemophilia A. Emicizumab is a bispecific monoclonal antibody mimicking factor VIIIa that provides a constant level of coagulation similar to that observed in minor haemophilia A patients whose factor VIII level is 10-15%. Although the correction of plasma coagulation in vivo is only partial, emicizumab strongly shortens the in vitro coagulation times involving the intrinsic pathway such as aPTT(activated partial thromboplastin time). The investigators will evaluate the effect of emicizumab on a coagulation test (Activating clotting time (ACT i-STAT Alinity)) used as a point of care device to monitor heparin therapies during cardiac surgeries (cardiopulmonary bypass) and cardiac catheterizations. Because ACT is activated through the intrinsic pathway, it may also be shortened by emicizumab. Prophylactic treatment with emicizumab would make it impossible to use ACT for heparin therapy in a hemophiliac patient benefiting from this treatment. The aim of this in vitro study is to assess the effect of emicizumab on the in vitro heparin-induced ACT increase in severe hemophilia A patients treated with emicizumab and in healthy volunteers (measurement on the i- STAT Alinity) thanks to in vitro blood spiking experiments. Some data have already been published with other ACT devices (Hemochron..) but never with the i-STAT Alinity device which uses a different technology and other reagents.

Conditions

Hemophilia A

Keywords

Activated Clotting Time; Hemophilia; Emicizumab

Outcome Measures

Primary Outcomes (1)

• Modification of ACT by emicizumab

  Modification of the in vitro heparin-induced ACT increase by emicizumab

  Day 0

Study Arms (2)

Severe hemophiliac patients under emicizumab

Diagnostic Test: ACT

Healthy volunteers

Diagnostic Test: ACT

Interventions

ACT DIAGNOSTIC_TEST

ACT will be measured : * after in vitro spiking with unfractionated heparin of blood samples from severe hemophilia A patients already treated with emicizumab * after in vitro spiking with unfractionated heparin with or without emicizumab of blood samples from healthy volunteers

Healthy volunteers; Severe hemophiliac patients under emicizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

see above

You may qualify if:

• severe hemophiliacs under emicizumab ( \> 4 weeks)

You may not qualify if:

• infusion of factor VIII \< 5 days
• patients refusing to participate in the study
• protected persons
• anticoagulants

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (1)

Grenoble University Hospital

Grenoble, 38700, France

RECRUITING

Related Publications (6)

• Mahlangu J, Oldenburg J, Paz-Priel I, Negrier C, Niggli M, Mancuso ME, Schmitt C, Jimenez-Yuste V, Kempton C, Dhalluin C, Callaghan MU, Bujan W, Shima M, Adamkewicz JI, Asikanius E, Levy GG, Kruse-Jarres R. Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors. N Engl J Med. 2018 Aug 30;379(9):811-822. doi: 10.1056/NEJMoa1803550.

  PMID: 30157389 BACKGROUND

• Lenting PJ. Laboratory monitoring of hemophilia A treatments: new challenges. Blood Adv. 2020 May 12;4(9):2111-2118. doi: 10.1182/bloodadvances.2019000849.

  PMID: 32396619 BACKGROUND

• Lowe A, Kitchen S, Jennings I, Kitchen DP, Woods TAL, Walker ID. Effects of Emicizumab on APTT, FVIII assays and FVIII Inhibitor assays using different reagents: Results of a UK NEQAS proficiency testing exercise. Haemophilia. 2020 Nov;26(6):1087-1091. doi: 10.1111/hae.14177. Epub 2020 Oct 23.

  PMID: 33094895 BACKGROUND

• Wahba A, Milojevic M, Boer C, De Somer FMJJ, Gudbjartsson T, van den Goor J, Jones TJ, Lomivorotov V, Merkle F, Ranucci M, Kunst G, Puis L; EACTS/EACTA/EBCP Committee Reviewers. 2019 EACTS/EACTA/EBCP guidelines on cardiopulmonary bypass in adult cardiac surgery. Eur J Cardiothorac Surg. 2020 Feb 1;57(2):210-251. doi: 10.1093/ejcts/ezz267. No abstract available.

  PMID: 31576396 BACKGROUND

• Capdevila L, Frere C, Desvages M, Harroche A, Bally C, Abbes A, d'Oiron R, Frenzel L, Borgel D, Lasne D. Emicizumab does not interfere with the activated clotting time. Haemophilia. 2022 Mar;28(2):362-366. doi: 10.1111/hae.14497. Epub 2022 Jan 21.

  PMID: 35060654 BACKGROUND

• Isaacs J, Welsby IJ, Schroder JN, Onwuemene OA. Activated Coagulation Time and Hepcon Protamine Titration Device to Manage Unfractionated Heparin During Cardiopulmonary Bypass in a Hemophilia A Patient on Emicizumab. J Cardiothorac Vasc Anesth. 2021 Nov;35(11):3299-3302. doi: 10.1053/j.jvca.2020.08.058. Epub 2020 Aug 27.

  PMID: 32928650 BACKGROUND

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Raphaël MARLU, MD

  Grenoble Alpes University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Raphaël MARLU, MD

CONTACT

33476765487; rmarlu@chu-grenoble.fr

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2023
• First Posted: May 12, 2023
• Study Start: July 12, 2023
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: August 1, 2023

Record last verified: 2023-07

Locations

FR (1)