Prosthetic Joint Infections
Conditions
Keywords
Phase II, FIAU, Fialuridine, Prosthetic, Joint, Infection, PET-CT
Brief summary
This protocol will evaluate the sensitivity and specificity of \[124I\]FIAU as a diagnostic imaging agent for the detection of prosthetic joint infections in patients.
Interventions
RADIATION[124I]FIAU
This is a single dose study of 5 mCi \[124I\]FIAU in subjects presenting with pain in a prosthetic knee or hip joint. Subject will receive two PET-CT scans after \[124I\]FIAU injection.
Sponsors
BioMed Valley Discoveries, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males or females age \>18 years 2. Ability to provide informed consent 3. A plain anterior-posterior (AP) and frog leg lateral X-ray of the hip or knee within 6 weeks of enrollment 4. Need for operative intervention in the opinion of the surgeon to correct the pain in the prosthetic joint 5. Prosthetic joint implant that has been in site for more than 3 months prior to enrolment 6. Having adequate general health to be expected to tolerate surgery adn to survive for 6 months from the time of informed consent 7. Women must be either postmenopausal or surgically sterile 8. Ability to return for all study assessments 9. Clinically euthyroid, or on stable thyroid replacement therapy
Exclusion criteria
1. Subjects who are unable to comply with study requirements 2. Indication, in the opinion of the principal investigator, for urgent surgery that would preclude the time needed for PET-CT scanning 3. History of an inherited mitochondrial disorder (e.g., Leber's hereditary neuropathy; neuropathy; ataxia, retinitis pigmentosa and ptosis \[NARP\]; myoneurogenic gastrointestinal encephalopathy \[MNGIE\]; myocolonic epilepsy with ragged red fibers \[MERFF\]; and mitochondrial myopathy, encephalomyopathy, lactic acidosis and stroke-like syndrome \[MELAS\]) 4. Alanine aminotransferase (ALT) \>5x the upper limit of normal (ULN) OR aspartate aminotransferase (AST) \>5X ULN 5. Creatinine clearance \<30 mL/min 6. Body mass that exceeds the rating of the CT table 7. Hypersensitivity to iodine 8. Any condition that would put the subject at reasonable risk in the opinion of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estimate the Sensitivity and Specificity of [124I]FIAU | 30 hours | The sensitivity and specificity of \[124I\]FIAU in the detection of prosthetic joint infection was determined based on the correlation of the patient's infection status determined by an independent image reviewer and the infection status assessed by an adjudication committee. * Presence or absence of infection: Images were to be assessed and optimized on an ongoing basis. The single blinded reader was to assess independently the PET-CT images (attenuation corrected \[AC\] and non-AC PET plus the AC CT) and provide a diagnosis (infected or uninfected) using the chosen parameter(s) without knowing the results of the surgery. The radiology reviewer was not given any additional clinical information on the patient for reassessments relative to the initial reads. A separate central radiologist was to read the comparator X-rays independently for the presence or absence of infection. All pathology slides were to be read by a single pathologist. Local microbiology results were to be used. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Safety and Tolerability of [124I]FIAU | 30 +/- 2 days | Safety will be monitored throughout the study for all subjects. safety will be assessed by monitoring of adverse events,vital signs,physical exams, and clinical laboratory tests including CBC, serum chemistry. |
| Define PET-CT Interpretation Criteria That Best Differentiate Infected vs Non-infected Prosthetic Joints | 30 +/- 2 days | The efficacy of \[124I\]FIAU could not be established due to the non-specific nature of the PET-CT signals caused by the metal artifacts from the prosthesis and pronounced muscle uptake of FIAU. It was impossible to define image review parameters for diagnosis of prosthetic joint infection. |
| Understand the Prevalence of Prosthetic Joint Infection | 30 +/- 2 days | The trial failed primary outcome, and this secondary outcome was not analyzed |
Other
| Measure | Time frame | Description |
|---|---|---|
| Estimate the Sensitivity and Specificity of Plain X-ray in Detecting Prosthetic Joint Infection | 15 mins | The adjudication committee evaluation of a subject's infection status will be used as the standard of truth to which X-ray is compared. The trial failed primary outcome, and this secondary outcome was not analyzed. |
| Determine the Sensitivity and Specificity of [124I]FIAU vs. Plain X-ray in Detecting Prosthetic Joint Infection | 30 hours | The adjudication committee evaluation of a subject's infection status will be used as the standard of truth to which \[124I\]FIAU and X-ray are compared. The trial failed primary outcome, and this secondary outcome was not analyzed. |
| Explore Whether the Adjudication Committee Evaluation of a Subject's Infection Status Correlates With Either of the Two Proposed Published Standards | 30 +/- 2 days | An independent adjudication committee will assess the totality of clinical information from each subject and assign them a status of infected or uninfected. The subject's infection status will be compared with either of the two proposed published standards to determine whether it corelates with any of the current consensus definitions or diagnostic algorithms. The trial failed primary outcome, and this secondary outcome was not analyzed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| [124I]FIAU Single dose study of \[124I\]FIAU in patients presenting with pain in a prosthetic knee or hip joint who will undergo PET-CT scanning.
\[124I\]FIAU: This is a single dose study of 5 mCi \[124I\]FIAU in subjects presenting with pain in a prosthetic knee or hip joint. Subject will receive two PET-CT scans after \[124I\]FIAU injection. | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | [124I]FIAU |
|---|---|
| Age, Continuous | 64.1 years STANDARD_DEVIATION 9.11 |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 22 |
| serious Total, serious adverse events | 1 / 22 |
Outcome results
Primary
Estimate the Sensitivity and Specificity of [124I]FIAU
The sensitivity and specificity of \[124I\]FIAU in the detection of prosthetic joint infection was determined based on the correlation of the patient's infection status determined by an independent image reviewer and the infection status assessed by an adjudication committee. * Presence or absence of infection: Images were to be assessed and optimized on an ongoing basis. The single blinded reader was to assess independently the PET-CT images (attenuation corrected \[AC\] and non-AC PET plus the AC CT) and provide a diagnosis (infected or uninfected) using the chosen parameter(s) without knowing the results of the surgery. The radiology reviewer was not given any additional clinical information on the patient for reassessments relative to the initial reads. A separate central radiologist was to read the comparator X-rays independently for the presence or absence of infection. All pathology slides were to be read by a single pathologist. Local microbiology results were to be used.
Time frame: 30 hours
Population: Out of 23 enrolled, only 22 received the investigational drug. One subject withdrew.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| [124I]FIAU | Estimate the Sensitivity and Specificity of [124I]FIAU | 80 percentage of participants |
Secondary
Define PET-CT Interpretation Criteria That Best Differentiate Infected vs Non-infected Prosthetic Joints
The efficacy of \[124I\]FIAU could not be established due to the non-specific nature of the PET-CT signals caused by the metal artifacts from the prosthesis and pronounced muscle uptake of FIAU. It was impossible to define image review parameters for diagnosis of prosthetic joint infection.
Time frame: 30 +/- 2 days
Secondary
Evaluate the Safety and Tolerability of [124I]FIAU
Safety will be monitored throughout the study for all subjects. safety will be assessed by monitoring of adverse events,vital signs,physical exams, and clinical laboratory tests including CBC, serum chemistry.
Time frame: 30 +/- 2 days
Population: 22 received the investigational drug. A single IV injection of 5 mCi \[124I\]FIAU was well tolerated in patients presenting with pain in a prosthetic joint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| [124I]FIAU | Evaluate the Safety and Tolerability of [124I]FIAU | 15 participants with adverse events |
Secondary
Understand the Prevalence of Prosthetic Joint Infection
The trial failed primary outcome, and this secondary outcome was not analyzed
Time frame: 30 +/- 2 days
Other Pre-specified
Determine the Sensitivity and Specificity of [124I]FIAU vs. Plain X-ray in Detecting Prosthetic Joint Infection
The adjudication committee evaluation of a subject's infection status will be used as the standard of truth to which \[124I\]FIAU and X-ray are compared. The trial failed primary outcome, and this secondary outcome was not analyzed.
Time frame: 30 hours
Other Pre-specified
Estimate the Sensitivity and Specificity of Plain X-ray in Detecting Prosthetic Joint Infection
The adjudication committee evaluation of a subject's infection status will be used as the standard of truth to which X-ray is compared. The trial failed primary outcome, and this secondary outcome was not analyzed.
Time frame: 15 mins
Other Pre-specified
Explore Whether the Adjudication Committee Evaluation of a Subject's Infection Status Correlates With Either of the Two Proposed Published Standards
An independent adjudication committee will assess the totality of clinical information from each subject and assign them a status of infected or uninfected. The subject's infection status will be compared with either of the two proposed published standards to determine whether it corelates with any of the current consensus definitions or diagnostic algorithms. The trial failed primary outcome, and this secondary outcome was not analyzed.
Time frame: 30 +/- 2 days