EndocarditisPhase 1/2AnnIENCT02459613
Assessment of Radiolabeled rhAnnexin V-128 in Infective Endocarditis
A Phase 1/2 study testing 99mTc-Annexin V-128 SPECT in people with Endocarditis and Thrombosis, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Endocarditis, Thrombosis
- What is being tested?
- 99mTc-Annexin V-128 SPECT
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteFrance
- Study dates
- 5 Feb 2016to May 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Endocarditis, Thrombosis
- Being tested
- 99mTc-Annexin V-128 SPECT
- Keywords
- Radionuclide imaging, Annexin
- Medical subject headings
- Endocarditis, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
99mTc-Annexin V-128 SPECTDrug
| Study group | Role | What they receive |
|---|---|---|
| Imaging | Experimental | 99mTc Annexin V-128 SPECT Receives: Drug: 99mTc-Annexin V-128 SPECT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnostic sensitivity in infective endocarditis and atrial thrombus
Measured: up to 4 weeks
Secondary outcomes (2)
Diagnostic value (sensitivity and specificity) in infective endocarditis
Measured: up to 4 weeks
Diagnostic sensitivity in atrial thrombus
Measured: up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2015 (estimated)
- Study start5 Feb 2016
- Primary completionMay 2017
- Study completionMay 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for EndocarditisStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Collaborators
- Advanced Accelerator Applications
- Responsible party
- Sponsor
- Investigators
- Dominique Le Guludec, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02459613
- Sponsor's protocol ID
- C13-38
- Acronym
- AnnIE
- Status last verified
- Aug 2021
- First submitted
- 13 May 2015
- Last updated
- 26 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Benali K, Louedec L, Azzouna RB, Merceron O, Nassar P, Al Shoukr F, Petiet A, Barbato D, Michel JB, Sarda-Mantel L, Le Guludec D, Rouzet F. Preclinical validation of 99mTc-annexin A5-128 in experimental autoimmune myocarditis and infective endocarditis: comparison with 99mTc-HYNIC-annexin A5. Mol Imaging. 2014;13. doi: 10.2310/7290.2014.00049.
PubMed 25431156Rouzet F, Dominguez Hernandez M, Hervatin F, Sarda-Mantel L, Lefort A, Duval X, Louedec L, Fantin B, Le Guludec D, Michel JB. Technetium 99m-labeled annexin V scintigraphy of platelet activation in vegetations of experimental endocarditis. Circulation. 2008 Feb 12;117(6):781-9. doi: 10.1161/CIRCULATIONAHA.107.718114. Epub 2008 Jan 28.
PubMed 18227388Duval X, Iung B, Klein I, Brochet E, Thabut G, Arnoult F, Lepage L, Laissy JP, Wolff M, Leport C; IMAGE (Resonance Magnetic Imaging at the Acute Phase of Endocarditis) Study Group. Effect of early cerebral magnetic resonance imaging on clinical decisions in infective endocarditis: a prospective study. Ann Intern Med. 2010 Apr 20;152(8):497-504, W175. doi: 10.7326/0003-4819-152-8-201004200-00006.
PubMed 20404380Sarda-Mantel L, Coutard M, Rouzet F, Raguin O, Vrigneaud JM, Hervatin F, Martet G, Touat Z, Merlet P, Le Guludec D, Michel JB. 99mTc-annexin-V functional imaging of luminal thrombus activity in abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 2006 Sep;26(9):2153-9. doi: 10.1161/01.ATV.0000237605.25666.13. Epub 2006 Jul 20.
PubMed 16857952
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02459613
- Acronym / sponsor ID
- AnnIE / C13-38
- Conditions
- Endocarditis, Thrombosis
- Keywords
- Radionuclide imaging, Annexin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Collaborators
- Advanced Accelerator Applications
- Study start
- 5 Feb 2016 (actual)
- Primary completion
- May 2017 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 2 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Imaging | Experimental | Drug: 99mTc-Annexin V-128 SPECT99mTc Annexin V-128 SPECT |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- stable clinical status
- signed informed consent
- contraception in women of childhood potential
- definite ou possible endocarditis (modified Duke criteria)
- presence of atrial thrombosis evidenced by transesophageal echocardiography
Key exclusion criteria (5 listed)
- pregnant or lactating women
- contra-indication to both MRI and CT
- history of cardiac surgery in relation with the current episode
- (effective) antibiotic regimen for more than 15 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 99mTc-Annexin V-128 SPECT | Drug | Imaging |
Primary outcome
Diagnostic sensitivity in infective endocarditis and atrial thrombus
Time frame: up to 4 weeks
2 secondary outcomes
Diagnostic value (sensitivity and specificity) in infective endocarditis
Time frame: up to 4 weeks
Diagnostic sensitivity in atrial thrombus
Time frame: up to 4 weeks
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2021.
- Background: PubMed 25431156Benali K, Louedec L, Azzouna RB, Merceron O, Nassar P, Al Shoukr F, Petiet A, Barbato D, Michel JB, Sarda-Mantel L, Le Guludec D, Rouzet F. Preclinical validation of 99mTc-annexin A5-128 in experimental autoimmune myocarditis and infective endocarditis: comparison with 99mTc-HYNIC-annexin A5. Mol Imaging. 2014;13. doi: 10.2310/7290.2014.00049.
- Background: PubMed 18227388Rouzet F, Dominguez Hernandez M, Hervatin F, Sarda-Mantel L, Lefort A, Duval X, Louedec L, Fantin B, Le Guludec D, Michel JB. Technetium 99m-labeled annexin V scintigraphy of platelet activation in vegetations of experimental endocarditis. Circulation. 2008 Feb 12;117(6):781-9. doi: 10.1161/CIRCULATIONAHA.107.718114. Epub 2008 Jan 28.
- Background: PubMed 20404380Duval X, Iung B, Klein I, Brochet E, Thabut G, Arnoult F, Lepage L, Laissy JP, Wolff M, Leport C; IMAGE (Resonance Magnetic Imaging at the Acute Phase of Endocarditis) Study Group. Effect of early cerebral magnetic resonance imaging on clinical decisions in infective endocarditis: a prospective study. Ann Intern Med. 2010 Apr 20;152(8):497-504, W175. doi: 10.7326/0003-4819-152-8-201004200-00006.
- Background: PubMed 16857952Sarda-Mantel L, Coutard M, Rouzet F, Raguin O, Vrigneaud JM, Hervatin F, Martet G, Touat Z, Merlet P, Le Guludec D, Michel JB. 99mTc-annexin-V functional imaging of luminal thrombus activity in abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 2006 Sep;26(9):2153-9. doi: 10.1161/01.ATV.0000237605.25666.13. Epub 2006 Jul 20.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dominique Le Guludec, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 99mTc-Annexin V-128 SPECT in people with Endocarditis and Thrombosis, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic sensitivity in infective endocarditis and atrial thrombus (time frame: up to 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02459613, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2021.