Methotrexate as a Steroid-sparing Agent in Idiopathic Retroperitoneal Fibrosis: a Randomised, Multicenter Trial (FIPREDEX)

Medical Therapy in Idiopathic Retroperitoneal Fibrosis: a Multicenter, Randomized, Controlled Trial of Prednisone vs Low-dose Prednisone Plus Methotrexate

Chronic periaortitis is a clinico-pathological entity encompassing idiopathic retroperitoneal fibrosis and perianeurysmal retroperitoneal fibrosis. The treatment of this disease is generally based on the use of glucocorticoids, which are often effective. However, prolonged steroid treatments are usually needed to achieve a sustained remission; additionally, patients frequently develop disease relapses following treatment discontinuation, therefore they may be exposed to high cumulative doses of glucocorticoids.

Preliminary data reported in the literature show that methotrexate may be effective in combination with prednisone for retroperitoneal fibrosis. In addition, methotrexate is often used as a steroid-sparing agent in different inflammatory diseases.

The aim of this study is to evaluate whether a treatment with low-dose prednisone plus methotrexate is non-inferior to conventional dose-prednisone in achieving remission in retroperitoneal fibrosis patients.

Study Overview

• Status: Unknown
• Conditions: Idiopathic Retroperitoneal Fibrosis; Perianeurysmal Retroperitoneal Fibrosis; Chronic Periaortitis
• Intervention / Treatment: Drug: Prednisone; Drug: Methotrexate+Prednisone

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Carlo Buzio, MD; Phone Number: +39 0521 702345; Email: carlo.buzio@unipr.it
• Study Contact Backup: Name: Augusto Vaglio, MD, PhD; Phone Number: +39 0521 702345; Email: augusto.vaglio@virgilio.it

Study Locations

• Italy
  • Parma, Italy, 43126
    • Recruiting
    • Nephrology Unit, University Hospital of Parma
    • Contact: Augusto Vaglio, MD PhD; Phone Number: +39 0521 702345; Email: augusto.vaglio@virgilio.it
    • Principal Investigator: Augusto Vaglio, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• New diagnosis of idiopathic retroperitoneal fibrosis or chronic periaortitis; written informed consent

Exclusion Criteria:

• Secondary forms of retroperitoneal fibrosis (e.g. drugs, surgery, neoplasms, infections)
• Previous medical therapy for retroperitoneal fibrosis
• Renal failure with creatinine >2 mg/dl which proved not to be reversible after ureteral decompression
• Hypersensitivity to the study drugs
• Pregnancy
• Active infections or malignant neoplasms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Prednisone	Drug: Prednisone
Experimental: Methotrexate+Prednisone	Drug: Methotrexate+Prednisone; Methotrexate will be added at a dose of 0.3 mg/kg/week (maximum dose, 20 mg/week, orally) to a reduced-dose prednisone regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Remission rate by the end of treatment

Secondary Outcome Measures

Outcome Measure
Treatment-related toxicity
Reduction in size of the retroperitoneal mass on CT/MRI scans
Rate of post-treatment relapses

Collaborators and Investigators

• Sponsor: University of Parma
• Investigators: Principal Investigator: Augusto Vaglio, MD, PhD, Parma University Hospital

Publications and helpful links

General Publications

• Vaglio A, Salvarani C, Buzio C. Retroperitoneal fibrosis. Lancet. 2006 Jan 21;367(9506):241-51. doi: 10.1016/S0140-6736(06)68035-5.
• van Bommel EF, Siemes C, Hak LE, van der Veer SJ, Hendriksz TR. Long-term renal and patient outcome in idiopathic retroperitoneal fibrosis treated with prednisone. Am J Kidney Dis. 2007 May;49(5):615-25. doi: 10.1053/j.ajkd.2007.02.268.
• Vaglio A, Palmisano A, Corradi D, Salvarani C, Buzio C. Retroperitoneal fibrosis: evolving concepts. Rheum Dis Clin North Am. 2007 Nov;33(4):803-17, vi-vii. doi: 10.1016/j.rdc.2007.07.013.
• Warnatz K, Keskin AG, Uhl M, Scholz C, Katzenwadel A, Vaith P, Peter HH, Walker UA. Immunosuppressive treatment of chronic periaortitis: a retrospective study of 20 patients with chronic periaortitis and a review of the literature. Ann Rheum Dis. 2005 Jun;64(6):828-33. doi: 10.1136/ard.2004.029793.

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Anticipated): May 1, 2012
• Study Completion (Anticipated): December 1, 2013

Study Registration Dates

• First Submitted: November 12, 2010
• First Submitted That Met QC Criteria: November 12, 2010
• First Posted (Estimate): November 15, 2010

Study Record Updates

• Last Update Posted (Estimate): November 15, 2010
• Last Update Submitted That Met QC Criteria: November 12, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: Methotrexate; Aorta; Prednisone; Retroperitoneal fibrosis; Inflammatory aneurysms
• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Retroperitoneal Fibrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Prednisone; Methotrexate
• Other Study ID Numbers: FARM79BKPY; 2008-007353-12 (EudraCT Number)