We aim to evaluate *v*3 integrin expression in proven COVID-19 infected patients with respiratory insufficiency and indicative findings on routine contrast-enhanced CT using [68Ga]Ga-DOTA-(RGD)2. If dysfunctional activated endothelium in the lung…
ID
Source
Brief title
Condition
- Viral infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the uptake of [68Ga]Ga-DOTA-(RGD)2 in the lesions
as quantified by PET/CT (SUVmean ±SD, SUVmax ±SD and SUVpeak ±SD).
Secondary outcome
1) spatial correlation (per lung segment) with ground-glass opacities,
consolidation, vessel size and other components of CORADS system
2) spatial correlation (per lung segment) with perfusion abnormalities as
measured by subtraction CT
3) quantitative correlation with blood counts and differentiation, ferritin,
D-dimer, CRP, liver enzyme panel (ALAT, ASAT, direct and indirect bilirubin,
alkaline phosphatase, gamma-GT, LDH), cytokines, as obtained by approved study
BioMarCo-19 (CMO 2020-6344)
4) correlation with the following clinical parameters: ICU admission,
mechanical ventilation parameters, oxygen demand, length of ICU stay (days),
length of hospital stay (days).
Additional study parameters are uptake in the myocardium and the
lung-to-background ratio (LBR).
Background summary
Patients diagnosed with COVID-19 present with markedly elevated D-dimer, ACE2,
leukopenia. When respiratory insufficiency develops, ventilation parameters
typically include high positive end-expiratory pressure (PEEP). These recent
findings strongly indicate dysfunctional activated endothelium of the lung
parenchyma.
Integrin *v*3 is over-expressed on activated endothelial cells. This expression
allows the interaction with extracellular matrix proteins through their
Arg-Gly-Asp (RGD) amino acid sequence. Previous studies at our institute
demonstrated the feasibility of molecular imaging to noninvasively quantitate
*v*3 integrin expression using PET/CT. Imaging activated endothelium in the
lung parenchyma might contribute to an improved understanding of the
pathophysiology in COVID-19.
Study objective
We aim to evaluate *v*3 integrin expression in proven COVID-19 infected
patients with respiratory insufficiency and indicative findings on routine
contrast-enhanced CT using [68Ga]Ga-DOTA-(RGD)2. If dysfunctional activated
endothelium in the lung parenchyma contributes to the progressive respiratory
insufficiency as frequently observed during COVID-19 infection, imaging *v*3
integrin expression using PET/CT could have potential as a clinical tool to
characterize patients at early stages during disease.
Study design
This is a prospective, observational non-randomized pilot study. Maximum 10
patients will undergo a [68Ga]Ga-DOTA-(RGD)2 PET/CT scan and CT-subtraction
scan in the same procedure. 10-minutes/bedposition static [68Ga]Ga-DOTA-(RGD)2
PET/CT scans of the thorax will be acquired starting at 60 minutes post
injection.
Study burden and risks
Toxicity tests have been performed in mice and no adverse events were seen.
Previous and published clinical studies with [68Ga]Ga-DOTA-(RGD)2 injection
showed no adverse events. The risks associated with the radiolabeled peptides
injection are in general low.
The combination of [68Ga]Ga-DOTA-(RGD)2 injection, low-dose CT and
CT-subtraction impose a radiation dose equivalent of 11.4 mSv to the patient..
The addition of the [68Ga]Ga-DOTA-(RGD)2 injection PET/CT scan will not cause a
change in risk and will still be in the risk category as defined by the
International Commission on Radiation Protection. Because diagnostics and
treatment are not influenced by the outcome of this study, the patient will not
directly benefit from participation in this study.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
* A microbiologically proven SARS-CoV-19 infection
* Pulmonary involvement as demonstrated on recent (<1 week) chest CT
* Enrolled in the BioMarCo-19 study (CMO2020-6344)
* More than or equal to 18 years of age;
* Ability to provide written informed consent.
Exclusion criteria
* Contra-indication for PET:
o Pregnancy;
o Breast-feeding;
o Severe claustrophobia.
* Contra-indication for administration of iodine-containing contrast agents.
* Other serious illness, e.g. history of malignancies
* Estimated creatinine clearance * 30 mL/min according to the Cockcroft-Gault
formula (or local institutional standard method)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-001325-31-NL |
| CCMO | NL73551.091.20 |