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

NCT ID: NCT05856903

Last Updated: 2023-08-01

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 15 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-07-12
• Study Completion Date: 2025-03-31

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

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Severe hemophiliac patients under emicizumab

ACT

Intervention Type: 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

ACT

Intervention Type: 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

Interventions

ACT

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

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• severe hemophiliacs under emicizumab ( > 4 weeks)

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Grenoble

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Raphaël MARLU, MD

Role: PRINCIPAL_INVESTIGATOR

Grenoble Alpes University Hospital

Locations

Grenoble University Hospital

Grenoble, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Raphaël MARLU, MD

Role: CONTACT

rmarlu@chu-grenoble.fr

33476765487

Facility Contacts

Raphaël MARLU

Role: primary

RMarlu@chu-grenoble.fr

0476765487

References

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.

Reference Type: BACKGROUND

PMID: 30157389 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 32396619 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33094895 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31576396 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35060654 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32928650 (View on PubMed)

Other Identifiers

2023-A00897-38

Identifier Type: OTHER

Identifier Source: secondary_id

38RC23.0124

Identifier Type: -

Identifier Source: org_study_id