18F-GP1 PET-CT to Detect Bioprosthetic Aortic Valve Thrombosis

Aortic Valve Disease Clinical Trial

Official title:

18F-GP1 Positron Emission Tomography-computed Tomography to Detect Bioprosthetic Aortic Valve Thrombosis; the Biothrombus Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04073875
• Other study ID #: E181981
• Status: Completed
• Start date: October 22, 2019
• Est. completion date: October 13, 2021

Study information

• Verified date: October 2021
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

18F-GP1 binds with high affinity to the glycoprotein IIb/IIIa receptors on activated platelets. 18F-GP1 PET-CT has recently demonstrated favourable safety, pharmacokinetic, biodistribution and diagnostic performance for the in vivo identification of venous and arterial thrombemboli.

Description:

Aortic stenosis is the most common reason for valvular interventions in the developed world, with rates projected to increase as the population ages. Aortic valve replacement remains the only recognised treatment available. Bioprostheses are far more common than mechanical prostheses, particularly with increasing rates of transcatheter heart valve use.

Bioprothetic valves are less durable than mechanical valves and are subject to deterioration which may lead to clinical heart failure and the need for re-intervention. Long-term results with surgical bioprostheses are well reported, with valve deterioration rates of less than 15% at 10 years. These data, however, rely on re-operation rather than echocardiographic measures, suggesting that the true incidence of structural valve deterioration is underestimated.

Valve thrombosis is increasingly recognised as a potential contributor to leaflet degeneration and has been detected in participants undergoing both surgical aortic valve replacement and transcatheter aortic valve implantation. The role of valve thrombosis as an early trigger for calcification and subsequent valve degeneration has not been addressed. The true incidence of valve thrombosis and its impact on clinical outcomes is unknown due to the lack of a sufficiently sensitive non-invasive imaging modality to detect early subclinical thrombosis. Current observational data suggests rates of 12 to 40%, based on computed tomography findings. There is a clinical need for a more sensitive non-invasive method of detecting valve thrombosis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: October 13, 2021
• Est. primary completion date: May 5, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• ability to give informed consent

• >1 month post-surgical or transcatheter aortic valve replacement

Exclusion Criteria:

• Inability to give informed consent

• Pregnancy or breastfeeding

• Contraindications to iodinated contrast

• Contraindications to anticoagulation

• Use of anticoagulants during the post-operative period prior to screening

• Extreme claustrophobia

• Chronic kidney disease (with estimated glomerular filtration rate <30 mL/min/1.73m2)

• Metastatic malignancy

• Inability to tolerate the supine position

Related Conditions & MeSH terms

• Aortic Valve Disease
• Thrombosis
• Thrombosis Cardiac

Intervention

Diagnostic Test:
• 18F-GP1
18F-GP1 PET-CT scan

Locations

Country	Name	City	State
United Kingdom	University of Edinburgh	Edinburgh

Sponsors (3)

Lead Sponsor	Collaborator
University of Edinburgh	British Heart Foundation, Life Molecular Imaging SA

Country where clinical trial is conducted

United Kingdom, 

References & Publications (9)

Chae SY, Kwon TW, Jin S, Kwon SU, Sung C, Oh SJ, Lee SJ, Oh JS, Han Y, Cho YP, Lee N, Kim JY, Koglin N, Berndt M, Stephens AW, Moon DH. A phase 1, first-in-human study of (18)F-GP1 positron emission tomography for imaging acute arterial thrombosis. EJNMMI Res. 2019 Jan 7;9(1):3. doi: 10.1186/s13550-018-0471-8. — View Citation

Chakravarty T, Søndergaard L, Friedman J, De Backer O, Berman D, Kofoed KF, Jilaihawi H, Shiota T, Abramowitz Y, Jørgensen TH, Rami T, Israr S, Fontana G, de Knegt M, Fuchs A, Lyden P, Trento A, Bhatt DL, Leon MB, Makkar RR; RESOLVE; SAVORY Investigators. Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study. Lancet. 2017 Jun 17;389(10087):2383-2392. doi: 10.1016/S0140-6736(17)30757-2. Epub 2017 Mar 19. — View Citation

Durko AP, Osnabrugge RL, Van Mieghem NM, Milojevic M, Mylotte D, Nkomo VT, Pieter Kappetein A. Annual number of candidates for transcatheter aortic valve implantation per country: current estimates and future projections. Eur Heart J. 2018 Jul 21;39(28):2635-2642. doi: 10.1093/eurheartj/ehy107. — View Citation

Johnston DR, Soltesz EG, Vakil N, Rajeswaran J, Roselli EE, Sabik JF 3rd, Smedira NG, Svensson LG, Lytle BW, Blackstone EH. Long-term durability of bioprosthetic aortic valves: implications from 12,569 implants. Ann Thorac Surg. 2015 Apr;99(4):1239-47. doi: 10.1016/j.athoracsur.2014.10.070. Epub 2015 Feb 4. — View Citation

Kim C, Lee JS, Han Y, Chae SY, Jin S, Sung C, Son HJ, Oh SJ, Lee SJ, Oh JS, Cho YP, Kwon TW, Lee DH, Jang S, Kim B, Koglin N, Berndt M, Stephens AW, Moon DH. Glycoprotein IIb/IIIa receptor imaging with (18)F-GP1 positron emission tomography for acute venous thromboembolism: an open-label, non-randomized, first-in-human phase 1 study. J Nucl Med. 2018 Jun 29. pii: jnumed.118.212084. doi: 10.2967/jnumed.118.212084. [Epub ahead of print] — View Citation

Lee N, Oh I, Chae SY, Jin S, Oh SJ, Lee SJ, Koglin N, Berndt M, Stephens AW, Oh JS, Moon DH. Radiation dosimetry of [(18)F]GP1 for imaging activated glycoprotein IIb/IIIa receptors with positron emission tomography in patients with acute thromboembolism. Nucl Med Biol. 2019 May - Jun;72-73:45-48. doi: 10.1016/j.nucmedbio.2019.07.003. Epub 2019 Jul 10. — View Citation

Lohrke J, Siebeneicher H, Berger M, Reinhardt M, Berndt M, Mueller A, Zerna M, Koglin N, Oden F, Bauser M, Friebe M, Dinkelborg LM, Huetter J, Stephens AW. (18)F-GP1, a Novel PET Tracer Designed for High-Sensitivity, Low-Background Detection of Thrombi. J Nucl Med. 2017 Jul;58(7):1094-1099. doi: 10.2967/jnumed.116.188896. Epub 2017 Mar 16. — View Citation

Makkar RR, Fontana G, Jilaihawi H, Chakravarty T, Kofoed KF, De Backer O, Asch FM, Ruiz CE, Olsen NT, Trento A, Friedman J, Berman D, Cheng W, Kashif M, Jelnin V, Kliger CA, Guo H, Pichard AD, Weissman NJ, Kapadia S, Manasse E, Bhatt DL, Leon MB, Søndergaard L. Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves. N Engl J Med. 2015 Nov 19;373(21):2015-24. doi: 10.1056/NEJMoa1509233. Epub 2015 Oct 5. — View Citation

Rodriguez-Gabella T, Voisine P, Puri R, Pibarot P, Rodés-Cabau J. Aortic Bioprosthetic Valve Durability: Incidence, Mechanisms, Predictors, and Management of Surgical and Transcatheter Valve Degeneration. J Am Coll Cardiol. 2017 Aug 22;70(8):1013-1028. doi: 10.1016/j.jacc.2017.07.715. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of 18F-GP1 PET-CT bioprosthetic aortic valve uptake	Prevalence of 18F-GP1 PET-CT bioprosthetic aortic valve uptake as measured by standardised uptake values.	2 years
Primary	Intensity of 18F-GP1 PET-CT activity in bioprosthetic aortic valve thrombus	Intensity of 18F-GP1 PET-CT activity in bioprosthetic aortic valve thrombus compared to blood pool as measured by standardised uptake values.	2 years
Secondary	18F-GP1 PET-CT bioprosthetic aortic valve uptake in patients with thrombus.	18F-GP1 PET-CT bioprosthetic aortic valve uptake after 3 months in patients with evidence of thrombus at baseline as measured by standardised uptake values.	2 years