Aprotinine et Xie cardiaque

…le retour ?

Mangano DT et al. N Engl J Med. 2006;354:353-65

Aprotinine

Aprotinine

Diminution des hémorragies massives et de la mortalité de 50% (Aprotinine vs ac tranexanique

Diminution de la mortalité de 50% (Aprotinine vs ac tranexanique)

Augmentation de la mortalité par 2,5

Aprotinine • Product:

– Injectable solution (0.5 Mio KIU/vial)

– Antifibrinolytic properties

• Indication:

Aprotinin is indicated for “Prophylactic use to reduce blood loss and blood transfusion in

adult patients who are at high risk of major blood loss undergoing isolated

cardiopulmonary bypass graft surgery (i.e. CABG that is not combined with other

cardiovascular surgery)”

3 conditions for aprotinin MA*

• Submission of an updated RMP**: referring to the agreed products’ safety concerns and their risk minimisation which includes a direct healthcare professional communication

• Conduct of a registry • Restricted distribution: aprotinin available only to centres that

perform cardiac surgery on cardio-pulmonary bypass and that commit to participate in the registry

*MA: Marketing Authorization = AMM **RMP: Risk Management Plan = Plan de Gestion des Risques

What is the NAPaR ?

NAPaR = Nordic Aprotinin Patient Registry

• The NAPaR) is a non-interventional Post-Authorisation Safety Study (PASS)

• A registry is to be conducted to monitor the pattern of use of aprotinin

* The Pharmacovigilance Risk Assessment Committee (PRAC) is the European Medicines Agency's (EMA) committee responsible for assessing and monitoring the safety of human medicines.

Mandatory Pharmacovigilance Risk Assessment Committee (PRAC)* endorsed protocol in

March 2015

Record on patients information exposed to aprotinin at cardiac surgery centres in

participating countries

Easy-to-use web-based database (“eCRF”)

Duration of study: at least three years or 12,000 patients… and the decision to terminate

the Registry will be taken based on agreement with the PRAC

The NAPaR in Europe

Countries:

Countries Active sites First included

patient Nbre of patients

SE 4 02/2016 122

UK 31 03/2016 1 858

DE 6 02/2017 259

AT 1 09/2017 4

FI 1 05/2018 4

2 247 patients

Status on September 6, 2018:

Active

Achieve regulatory acceptance

Pending regulatoy validation

Approved by CPP (France)

Approved centers (n=7)

Aprotinin

• Full « Royston » : 2 million KIU load, 2 million

KIU pump prime, and 0.5 million KIU/h

continuous infusion

• Half « Roytson »

Objectif de recrutement : 3 patients /mois….

Conclusion

• Registre en France : étude multicentrique

• Réintroduction de l’Aprotinine ?

– Chirurgies à haut risque

– Patients à haut risque

– Intérêt médico-économique

Remerciements

Pr JL Fellahi