68Ga-NODAGA-RGD PET in Patients With an Occluded Coronary Artery

NCT ID: NCT04871217

Last Updated: 2022-03-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-04

Study Completion Date

2023-12-31

Brief Summary

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Background: In patients with coronary artery disease, acute or chronic coronary artery occlusion is associated with various degrees of ischemic myocardial injury and left ventricle dysfunction. The integrin αVβ3 plays a role in angiogenesis, i.e. formation of new capillaries from pre-existing blood vessels that is increased during repair of ischemic myocardial injury. 68Ga-NODAGA-RGD is a radiopharmaceutical for positron emission tomography (PET) imaging of αVβ3 integrin expression.

Aim: This study aims at evaluating the feasibility of imaging myocardial αVβ3 integrin expression using 68-Ga-NODAGA-RGD PET and whether 68Ga-NODAGA-RGD uptake is associated with myocardial contractile function in patients with an acute or chronic coronary artery occlusion.

Study design: An academic, prospective, open-label study in 60 patients with an acute or chronic coronary occlusion.

Study population: 30 patients with an ST-elevation acute myocardial infarction weeks and left ventricular ejection fraction \<50%. 30 patients with planned percutaneous re-opening of a chronic coronary total occlusion and left ventricular ejection fraction \<50%.

Study procedures: Patients will undergo cardiac 68Ga-NODAGA-RGD PET within 3 to 14 days after an ST-elevation acute myocardial infarction or within 4 weeks before and 2 weeks after planned percutaneous re-opening of chronic coronary total occlusion. Myocardial perfusion reserve will be evaluated in patients with chronic total occlusion by PET. Echocardiography will be performed at the time of PET imaging and repeated 6 months later to evaluate global and regional left ventricle contractile function. Data on relevant cardiovascular clinical history and blood sample will be obtained at imaging visits. Cardiac events will be evaluated after two years.

End-points: Primary: Myocardial uptake of 68-Ga-NODAGA-RGD after an acute myocardial infarction or before and after opening of chronic coronary occlusion. Secondary: Global and regional left ventricle systolic function. Blood biomarkers of myocardial injury and heart failure. Myocardial perfusion reserve. Adverse cardiac events including death, myocardial infarction, unstable angina pectoris, repeat revascularization and heart failure hospitalizations.

Detailed Description

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Background: In patients with coronary artery disease, acute or chronic coronary artery occlusion is associated with various degrees of ischemic myocardial injury and left ventricle dysfunction. The integrin αVβ3 plays a role in angiogenesis (Brooks 1994), i.e. formation of new capillaries from pre-existing blood vessels that is increased during repair of ischemic myocardial injury (Meoli 2004, Higuchi 2008, Sherif 2012, Sun 2003, Jenkins 2017). 68Ga-NODAGA-RGD is a radiopharmaceutical for positron emission tomography (PET) imaging of αVβ3 integrin expression (Grönman 2017, Buchegger 2011, Pohle 2012, Gnesin 2017).

Aim: This study aims at evaluating the feasibility of imaging myocardial αVβ3 integrin expression using 68-Ga-NODAGA-RGD PET and whether 68Ga-NODAGA-RGD uptake is associated with myocardial contractile function in patients with an acute or chronic coronary artery occlusion.

Study design: An investigator-initiated, prospective, open-label study in 60 patients with an acute or chronic coronary occlusion.

Study population: 30 patients with an ST-elevation acute myocardial infarction weeks and left ventricular ejection fraction \<50%. 30 patients with planned percutaneous re-opening of a chronic coronary total occlusion and left ventricular ejection fraction \<50%.

Study procedures: Patients will undergo cardiac 68Ga-NODAGA-RGD PET within 3 to 14 days after an ST-elevation acute myocardial infarction or within 4 weeks before and 2 weeks after planned percutaneous re-opening of chronic coronary total occlusion. Myocardial perfusion reserve will be evaluated in patients with chronic total occlusion by PET myocardial perfusion imaging. Complete echocardiography will be performed at the time of PET imaging and repeated 6 months later to evaluate global and regional left ventricle contractile function. Data on relevant cardiovascular clinical history and blood sample will be obtained at imaging visits. Cardiac events will be evaluated after two years.

Primary end-point: Myocardial uptake of 68-Ga-NODAGA-RGD after an acute myocardial infarction or before and after opening of chronic coronary occlusion. Secondary end-points: Global and regional left ventricle systolic function. Blood biomarkers of myocardial injury (troponin) and heart failure (pro-BNP). Myocardial perfusion reserve. Adverse cardiac events including death, myocardial infarction, unstable angina pectoris, repeat revascularization and heart failure hospitalizations.

Sample size: This is an exploratory study and formal power calculation cannot be performed.

Ethical aspects: The study conforms to the World Medical Association Declaration of Helsinki. Written statement will be obtained from the ethics committee (the Ethical Board of the South-Western Finland). Permissions from regulatory authorities (the Finnish Medicines Agency Fimea) and the Turku University Hospital for conducting the study will be obtained. Signed and dated informed consent will be obtained from patients before conducting any study specific procedures.

Conditions

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Coronary Artery Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Acute ST-elevation myocardial infarction or chronic coronary artery occlusion

68-Ga-NODAGA-RGD PET after acute ST-elevation myocardial infarction or before and after re-opening of a chronic coronary artery occlusion

Group Type EXPERIMENTAL

68Ga-NODAGA-RGD PET-imaging

Intervention Type DIAGNOSTIC_TEST

Patients will undergo cardiac 68Ga-NODAGA-RGD PET in order to detect myocardial αVβ3 integrin expression 3-14 days after an acute myocardial infarction or within 4 weeks before and 2 weeks after re-opening of chronic coronary occlusion. Echocardiography of cardiac function will be performed at the time of PET imaging and repeated 6 months later.

Interventions

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68Ga-NODAGA-RGD PET-imaging

Patients will undergo cardiac 68Ga-NODAGA-RGD PET in order to detect myocardial αVβ3 integrin expression 3-14 days after an acute myocardial infarction or within 4 weeks before and 2 weeks after re-opening of chronic coronary occlusion. Echocardiography of cardiac function will be performed at the time of PET imaging and repeated 6 months later.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* ST-elevation acute myocardial infarction within 3-14 days
* Planned elective percutaneous revascularization of angiographically documented coronary chronic total occlusion (CTO)
* Left ventricular ejection fraction \< 50% when hospitalized for index acute myocardial infarction or within 12 months before planned revascularization of coronary CTO
* Provision of signed and dated informed consent prior to study specific procedures

Exclusion Criteria

* Current unstable angina
* Significant valvular heart disease
* NYHA IV heart failure symptoms
* Severe untreated hypertension (\>180/110 mmHg)
* Female not post-menopausal
* Contraindications for adenosine infusion (in patients with CTO):
* Severe renal failure (estimated glomerular filtration rate \< 30 ml/min)
* Atrial fibrillation with ventricular response \> 110 bpm
* No acoustic window for left ventricle assessment by echocardiography
* Previous cardiac surgery
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Lausanne Hospitals

OTHER

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role collaborator

Turku University Hospital

OTHER_GOV

Sponsor Role lead

Responsible Party

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Antti Saraste

MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Antti Saraste, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Turku University Hospital

Locations

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Turku University Hospital

Turku, , Finland

Site Status RECRUITING

Leiden Medical Center

Leiden, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

University of Lausanne Hospitals

Lausanne, , Switzerland

Site Status RECRUITING

Countries

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Finland Netherlands Switzerland

Central Contacts

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Antti Saraste, MD, PhD

Role: CONTACT

+35823130000

Facility Contacts

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Antti Saraste, MD, PhD

Role: primary

+3582313000

John Prior, MD, PhD

Role: primary

References

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Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science. 1994 Apr 22;264(5158):569-71. doi: 10.1126/science.7512751.

Reference Type BACKGROUND
PMID: 7512751 (View on PubMed)

Buchegger F, Viertl D, Baechler S, Dunet V, Kosinski M, Poitry-Yamate C, Ruegg C, Prior JO. 68Ga-NODAGA-RGDyK for alphavbeta3 integrin PET imaging. Preclinical investigation and dosimetry. Nuklearmedizin. 2011;50(6):225-33. doi: 10.3413/Nukmed-0416-11-06. Epub 2011 Oct 11.

Reference Type BACKGROUND
PMID: 21989840 (View on PubMed)

Gronman M, Tarkia M, Kiviniemi T, Halonen P, Kuivanen A, Savunen T, Tolvanen T, Teuho J, Kakela M, Metsala O, Pietila M, Saukko P, Yla-Herttuala S, Knuuti J, Roivainen A, Saraste A. Imaging of alphavbeta3 integrin expression in experimental myocardial ischemia with [68Ga]NODAGA-RGD positron emission tomography. J Transl Med. 2017 Jun 19;15(1):144. doi: 10.1186/s12967-017-1245-1.

Reference Type BACKGROUND
PMID: 28629432 (View on PubMed)

Higuchi T, Bengel FM, Seidl S, Watzlowik P, Kessler H, Hegenloh R, Reder S, Nekolla SG, Wester HJ, Schwaiger M. Assessment of alphavbeta3 integrin expression after myocardial infarction by positron emission tomography. Cardiovasc Res. 2008 May 1;78(2):395-403. doi: 10.1093/cvr/cvn033. Epub 2008 Feb 6.

Reference Type BACKGROUND
PMID: 18256073 (View on PubMed)

Jenkins WS, Vesey AT, Stirrat C, Connell M, Lucatelli C, Neale A, Moles C, Vickers A, Fletcher A, Pawade T, Wilson I, Rudd JH, van Beek EJ, Mirsadraee S, Dweck MR, Newby DE. Cardiac alphaVbeta3 integrin expression following acute myocardial infarction in humans. Heart. 2017 Apr;103(8):607-615. doi: 10.1136/heartjnl-2016-310115. Epub 2016 Dec 7.

Reference Type BACKGROUND
PMID: 27927700 (View on PubMed)

Meoli DF, Sadeghi MM, Krassilnikova S, Bourke BN, Giordano FJ, Dione DP, Su H, Edwards DS, Liu S, Harris TD, Madri JA, Zaret BL, Sinusas AJ. Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction. J Clin Invest. 2004 Jun;113(12):1684-91. doi: 10.1172/JCI20352.

Reference Type BACKGROUND
PMID: 15199403 (View on PubMed)

Pohle K, Notni J, Bussemer J, Kessler H, Schwaiger M, Beer AJ. 68Ga-NODAGA-RGD is a suitable substitute for (18)F-Galacto-RGD and can be produced with high specific activity in a cGMP/GRP compliant automated process. Nucl Med Biol. 2012 Aug;39(6):777-84. doi: 10.1016/j.nucmedbio.2012.02.006. Epub 2012 Mar 22.

Reference Type BACKGROUND
PMID: 22444238 (View on PubMed)

Sherif HM, Saraste A, Nekolla SG, Weidl E, Reder S, Tapfer A, Rudelius M, Higuchi T, Botnar RM, Wester HJ, Schwaiger M. Molecular imaging of early alphavbeta3 integrin expression predicts long-term left-ventricle remodeling after myocardial infarction in rats. J Nucl Med. 2012 Feb;53(2):318-23. doi: 10.2967/jnumed.111.091652.

Reference Type BACKGROUND
PMID: 22302965 (View on PubMed)

Sun M, Opavsky MA, Stewart DJ, Rabinovitch M, Dawood F, Wen WH, Liu PP. Temporal response and localization of integrins beta1 and beta3 in the heart after myocardial infarction: regulation by cytokines. Circulation. 2003 Feb 25;107(7):1046-52. doi: 10.1161/01.cir.0000051363.86009.3c.

Reference Type BACKGROUND
PMID: 12600920 (View on PubMed)

Gnesin S, Mitsakis P, Cicone F, Deshayes E, Dunet V, Gallino AF, Kosinski M, Baechler S, Buchegger F, Viertl D, Prior JO. First in-human radiation dosimetry of 68Ga-NODAGA-RGDyK. EJNMMI Res. 2017 Dec;7(1):43. doi: 10.1186/s13550-017-0288-x. Epub 2017 May 18.

Reference Type BACKGROUND
PMID: 28523582 (View on PubMed)

Nammas W, Paunonen C, Teuho J, Siekkinen R, Luoto P, Kakela M, Hietanen A, Viljanen T, Dietz M, Prior JO, Li XG, Roivainen A, Knuuti J, Saraste A. Imaging of Myocardial alphavbeta3 Integrin Expression for Evaluation of Myocardial Injury After Acute Myocardial Infarction. J Nucl Med. 2024 Jan 2;65(1):132-138. doi: 10.2967/jnumed.123.266148.

Reference Type DERIVED
PMID: 37973184 (View on PubMed)

Other Identifiers

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T02/011/18

Identifier Type: -

Identifier Source: org_study_id

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