Early Discontinuation of Steroid Treatment in Negative FDG-PET/CT Patients With Idiopathic Retroperitoneal Fibrosis

Idiopathic Retroperitoneal Fibrosis Clinical Trial

— METRO  

Official title:

Early Discontinuation of Steroid Treatment in Negative FDG-PET/CT Patients With Idiopathic Retroperitoneal Fibrosis. A Prospective Multicentric Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05428826
• Other study ID #: APHP210082
• Status: Recruiting
• Phase: Phase 4
• Start date: November 25, 2022
• Est. completion date: November 25, 2028

Study information

• Verified date: January 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Karim SACRE
• Phone: 01.40.25.60.19
• Email: karim.sacre[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Adult patients with a diagnosis of idiopathic retroperitoneal fibrosis Prospective multicentric cohort study Intervention : administration of prednisone during 9 to 21 months at 1mg/kg/day at inclusion.

Description:

At baseline visit: Eligible patients will be screen during a standard visit care (consultation or hospitalization). A clinical examination, an abdominal CT scan, blood and urine biological tests will be performed.

At inclusion visit: After verification of inclusion and non inclusion criteria, if the patient meets the eligibility criteria, the investigator, will provide the patient with information and details regarding the trial. The consent is obtained and signed after a reflection period of 30 minutes.

The following procedure will be scheduled within 7 days:

• 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET/CT) (pregnancy test if mandatory)

• Specimens for the biocollection Patients with positive FDG PET/CT (hypermetabolism grade II or III) at M0 will receive oral steroids (prednisone) at 1mg/kg/day during 1 month and then the dose will be tapered to obtain <10mg/day at 6 months and <7,5mg/day at 9 months.

Patients with a negative FDG-PET/CT (hypermetabolism grade 0 or I) at M0 will be excluded of the study.

Follow-up visits : M6, M9,M12,M15,M21, relapse At M6, M12, and M15: During these visits clinical examination (blood pressure measurement, body temperature, heart rate, weight and clinical signs or symptoms related to IRF) will be performed. An abdominal CT scan may be performed as part of the care depending on the clinician's judgment. Glucocorticoid compliance and tapering, concomitant medications and adverse events (including serious cardiovascular adverse events) will be assessed and recorded. A nurse will collect blood and urine.

At M9, M21 or relapse : During these visits clinical examination, an abdominal CT scan, a FDG-PET/CT blood and urine biological tests will be performed.

At M9: The patients who failed to reach remission at M9 are considered as treatment failure and will be treated on best medical judgment by the investigator and excluded to the study. The patients who had a dose of prednisone ≥7,5mg / day at M9 will also be excluded to the study.

Patients who achieved remission at M9 and have a retroperitoneal fibrosis visual score grade 0 or I under a dose of prednisone <7,5mg / day will discontinue steroids treatment.

Patients who achieved remission at M9 and have a retroperitoneal fibrosis visual score grade II or III under a dose of prednisone <7,5mg / day will continue steroids treatment at the actual dose (medical judgment).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 41
• Est. completion date: November 25, 2028
• Est. primary completion date: November 25, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient over 18 years old

• New onset or untreated relapsing of active idiopathic retroperitoneal fibrosis (IRF) defined by the association of:

• Related-disease symptoms (Appendix 17.2) or elevated CRP level (>20 mg/l) AND

• Retroperitoneal peri-aortic mass that surrounds the abdominal vessels on CT-scan

Exclusion Criteria:

• Secondary retroperitoneal fibrosis including drug-related retroperitoneal fibrosis, active infections (such as tuberculosis) or malignancies, systemic vasculitis (such as Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis), Erdheim-Chester disease (Appendix 17.3),patients with IgG4 disease may be enrolled

• Contraindication to perform FDG-PET/CT,

• Contraindication to perform CT scan with injection of contrast agent,

• Contraindication to treatment by prednisone

• Active infection

• Acute or chronic liver disease that is deemed sufficiently severe to impair their ability to participate in the trial,

• Active or history of malignancy in last 5 years. Individuals with squamous cell or basal cell skin carcinomas and individuals with cervical carcinoma in situ may be enrolled if they have received curative surgical treatment,

• Serum creatinine level greater than 400 µmol/L that cannot be attributed to underlying IRF,

• Live vaccination received from 4 weeks before inclusion,

• Inhaled glucocorticoids (except for patients with documented asthma),

• Any previous treatment with rituximab, methotrexate, alemtuzumab, cyclophosphamide, azathioprine, mycophenolate mofetil, infliximab, adalimumab, etanercept within the past 3 months,

• Pregnancy or breastfeeding,

• Non-affiliation to a social security regime,

• Subject deprived of freedom, subject under a legal protective measure

• Refusal to participate

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Retroperitoneal Fibrosis
• Retroperitoneal Fibrosis

Intervention

Drug:
• Prednisone
Phase 4 Prednisone Dose : 1mg/kg/day at inclusion Route of administration : oral Duration of treatment: 9 to 21 months.

Locations

Country	Name	City	State
France	Médecine Interne	Agen
France	Médecine interne et maladies infectieuses - GH Sud Haut Lévêque	Bordeaux
France	Médecine interne - Ambroise Paré	Boulogne-Billancourt
France	Médecine interne	Brest
France	Médecine interne - Henri-Mondor	Créteil
France	Médecine interne et immunologie clinique - Dijon	Dijon
France	Médecine interne - Lille	Lille
France	Médecine Interne - La Timone	Marseille
France	Médecine Interne - Bichat	Paris
France	Médecine interne - Cochin	Paris
France	Médecine interne - Saint Antoine	Paris
France	Médecine Interne, Vascularites et Myosites - La Pitié Salpêtrière	Paris
France	Médecine vasculaire - HEGP	Paris
France	Néphrologie - Bichat	Paris
France	Médecine interne - Delafontaine	Saint-Denis

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To compare the cumulative IRF relapse rate 12 months after discontinuation of steroids.	The primary endpoint is the cumulate IRF relapse rate 12 months after discontinuation of steroids.; The diagnosis of IRF relapse is based on the association of a clinical or biological criterion with a radiological criterion (i.e. composite criteria): Clinical or biological criteria; recurrent or new-onset disease related symptoms; increase in C-reactive protein (CRP) >20mg/L without other cause; And a Radiological criterion o increased of retroperitoneal fibrosis size as compared with the CT scan performed at remission.; The primary endpoint will be centrally adjudicated.	12 months after discontinuation of steroids
Secondary	To analyze the characteristics of hypermetabolism of IRF in FDG-PET/CT and their evolution at inclusion	Visual grades of retroperitoneal fibrosis FDG uptake as compared to liver FDG uptake (which consist of one item that yields a score of 0 to III),	at inclusion
Secondary	To analyze the characteristics of hypermetabolism of IRF in FDG-PET/CT and their evolution at inclusion	maximal standardized uptake value (SUVmax) within the retroperitoneal fibrosis (regions of interest- ROI) at diagnosis (M0)	at inclusion
Secondary	To analyze the characteristics of hypermetabolism of IRF in FDG-PET/CT and their evolution at inclusion	Metabolic volume (i.e. ratio of metabolically active volume (MAV) to global lesion volume) of retroperitoneal fibrosis FDG uptake at diagnosis	at inclusion
Secondary	To analyze the characteristics of hypermetabolism of IRF in FDG-PET/CT and their evolution at remission (M9)	Visual grades of retroperitoneal fibrosis fluorodeoxyglucose uptake as compared to liver fluorodeoxyglucose uptake (which consist of one item that yields a score of 0 to 3) A 0 significate an lack of FDG binding and a 3 an FDG uptake greater than liver uptakesignificate.	9 months after the inclusion
Secondary	To analyze the characteristics of hypermetabolism of IRF in FDG-PET/CT and their evolution at remission (M9)	maximal standardized uptake value (SUVmax) within the retroperitoneal fibrosis (regions of interest- ROI) at remission (M9)	9 months after the inclusion
Secondary	To analyze the characteristics of hypermetabolism of IRF in FDG-PET/CT and their evolution at remission (M9)	Metabolic volume (i.e. ratio of metabolically active volume (MAV) to global lesion volume) of retroperitoneal fibrosis FDG uptake remission (M9)	9 months after the inclusion
Secondary	To analyze the characteristics of hypermetabolism of IRF in FDG-PET/CT and their evolution at M21	Visual grades of retroperitoneal fibrosis FDG uptake as compared to liver FDG uptake (which consist of one item that yields a score of 0 to III)	21 months after the inclusion
Secondary	To analyze the characteristics of hypermetabolism of IRF in FDG-PET/CT and their evolution at M21	maximal standardized uptake value (SUVmax) within the retroperitoneal fibrosis (regions of interest- ROI) at M21	21 months after the inclusion
Secondary	To analyze the characteristics of hypermetabolism of IRF in FDG-PET/CT and their evolution at M21	Metabolic volume (i.e. ratio of metabolically active volume (MAV) to global lesion volume) of retroperitoneal fibrosis FDG uptake at M21	21 months after the inclusion
Secondary	To analyze the characteristics of hypermetabolism of IRF in FDG-PET/CT and their evolution at relapse	Visual grades of retroperitoneal fibrosis FDG uptake as compared to liver FDG uptake (which consist of one item that yields a score of 0 to III)	between inclusion and 21 months after the inclusion
Secondary	To analyze the characteristics of hypermetabolism of IRF in FDG-PET/CT and their evolution at relapse	maximal standardized uptake value (SUVmax) within the retroperitoneal fibrosis (regions of interest- ROI) at relapse	between inclusion and 21 months after the inclusion
Secondary	To analyze the characteristics of hypermetabolism of IRF in FDG-PET/CT and their evolution at relapse	Metabolic volume (i.e. ratio of metabolically active volume (MAV) to global lesion volume) of retroperitoneal fibrosis FDG uptake at relapse	between inclusion and 21 months after the inclusion
Secondary	To assess the performance of hypermetabolism of IRF in FDG-PET/CT for diagnosis of disease activity,	Diagnostic performance of SUVmax for the disease activity	21 months after the inclusion
Secondary	To assess the performance of hypermetabolism of IRF in FDG-PET/CT for diagnosis of disease activity,	Diagnostic performance of MAV (area under the curve (AUC) and performance values for the Youden index) for the disease activity	21 months after the inclusion
Secondary	To compare at M21 the corticosteroids therapy - related adverse events between patients who continue or discontinue the treatment at M9.	Frequency of diabetes, severe infection, osteoporotic fracture and major cardiovascular events 12 months after remission (M21). Serious cardiovascular adverse events are defined as a composite of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death and will be assessed at M12,M15 and M21	21 months after the inclusion