Assessment of Radiolabeled rhAnnexin V-128 in Infective Endocarditis

Study Overview
=================
Brief Summary
-----------------
Intraluminal thrombi adherent to cardiac valves or atria share a common pathophysiology involving the aggregation of activated platelets with phosphatidylserine (PS) expression on the outer layer of the thrombus. They also share common complications, i.e. damages to the underlying myocardium and embolic risk related to thrombus fragmentation. The diagnostic work-up, currently relying on morphologic imaging alone (mainly echography), lacks sensitivity and does not allow to differentiate between active (renewal and growth activity) and quiescent (scarred) thrombus. It is therefore highly desirable to develop a new approach able to non-invasively provide insight on the biological activity of thrombi and to detect embolic events in a single exam. Annexin V is a 36 kDa endogenous glycoprotein which binds PS with nanomolar affinity. Radiolabeled Annexin V has been shown to provide molecular imaging of PS expressed by apoptotic cells or activated platelets. The ability of the imaging agent to bind mural thrombus has been established in vivo in a murine model of abdominal aortic aneurysm and ex vivo in human. It has been also shown that radiolabeled Annexin V allowed in vivo detection of vegetations and secondary pulmonary emboli with high sensitivity in various animal models of infective endocarditis. A radiolabeling kit of annexin V complying with GMP requirements has been developed (rhAnnexine V-128, Advanced Accelerator Applications - Atreus) and is currently available. AnniE is a single centre, proof of concept, interventional, open, non-randomized study aiming at evaluating the sensitivity of 99mTc-Annexin V-128 in the detection thrombus in comparison with reference imaging in patients presenting with either: 1/ infective endocarditis or 2/ atrial thrombus. The safety of the 99mTc-Annexin V-128 will be assessed in a first phase (10 first patients enrolled). Data in relation with safety of the imaging agent will be reviewed by an independent Data and Safety Monitoring Board (DSMB); in case of positive answer, the study will continue with a second phase. The data gathered in all patients (n=120) will be used to determine outcome measures.

Official Title
-----------------
Evaluation de la rhAnnexine V-128 radiomarquée Dans le Diagnostic de l'Endocardite Infectieuse, du Thrombus Atrial et de Leurs Complications Emboliques associées

Conditions
-----------------
Endocarditis, Thrombosis

Intervention / Treatment
-----------------
* Drug: 99mTc-Annexin V-128 SPECT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: stable clinical status signed informed consent contraception in women of childhood potential Endocarditis group: definite ou possible endocarditis (modified Duke criteria) Atrial thrombosis group: presence of atrial thrombosis evidenced by transesophageal echocardiography Exclusion Criteria: pregnant or lactating women contra-indication to both MRI and CT Endocarditis group: history of cardiac surgery in relation with the current episode (effective) antibiotic regimen for more than 15 days

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imaging<br>99mTc Annexin V-128 SPECT | Drug: 99mTc-Annexin V-128 SPECT<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic sensitivity in infective endocarditis and atrial thrombus |  | up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic value (sensitivity and specificity) in infective endocarditis |  | up to 4 weeks | 
| Diagnostic sensitivity in atrial thrombus |  | up to 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Radionuclide imaging, Annexin