Study of Sirolimus in Idiopathic Retroperitoneal Fibrosis

Prospective Study of Prednisone Versus Sirolimus in the Treatment of Idiopathic Retroperitoneal Fibrosis

Retroperitoneal fibrosis refers to a group of diseases characterized by hyperplasia of the fibrosclerotic tissues in the retroperitoneal space, which can compress the surrounding ureters and inferior vena cava and cause serious complications such as aortic aneurysm, renal failure, and even death. The lesion is diffuse and difficult to resect. corticosteroid is the first-line medication, but the recurrence rate of the disease is high, especially after dose reduction of corticosteroid. Therefore, the combined use of immunosuppressants is very important in preventing disease recurrence and reducing the toxic and side effects of long-term corticosteroid. Sirolimus plays dual roles in inhibiting lymphocyte activation and fibroblast proliferation. It is inferred from its mechanism that sirolimus is a good potential treatment option for idiopathic retroperitoneal fibrosis. Therefore, we conducted this RCT on patients with idiopathic retroperitoneal fibrosis to determine the efficacy and safety of sirolimus.

Study Overview

• Status: Recruiting
• Conditions: Retroperitoneal Fibrosis
• Intervention / Treatment: Drug: Sirolimus; Drug: Corticosteroid

Detailed Description

Retroperitoneal fibrosis refers to a group of diseases characterized by hyperplasia of the fibrosclerotic tissues in the retroperitoneal space, which mostly involve the abdominal aorta and iliac artery distal to the kidneys. The hyperplastic tissues can compress the surrounding ureters and inferior vena cava and cause serious complications such as aortic aneurysm, renal failure, and even death. There is no clear boundary between the lesion and its surrounding tissues. The lesion is diffuse and difficult to resect. corticosteroid is the first-line medication, but the recurrence rate of the disease is high, especially after dose reduction of corticosteroid. Therefore, the combined use of immunosuppressants is very important in preventing disease recurrence and reducing the toxic and side effects of long-term high- and medium-dose corticosteroid. In recent years, as the immunological characteristics of retroperitoneal fibrosis have gradually been recognized, some rheumatologists and immunologists have attempted to use immunosuppressants commonly used for autoimmune diseases in this population, including biologics. However, high-level evidences of evidence-based medicine such as randomized controlled trials (RCTs) were still lacking. Sirolimus plays dual roles in inhibiting T lymphocyte activation and fibroblast proliferation. It is inferred from its mechanism that sirolimus is a good potential treatment option for idiopathic retroperitoneal fibrosis. Therefore, we conducted this RCT on patients with idiopathic retroperitoneal fibrosis to determine the efficacy and safety of sirolimus.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Hui Gao, Doctor; Phone Number: 8613811833264; Email: gh841017@126.com
• Study Contact Backup: Name: Zhan-guo Li, Professor; Phone Number: 8610-88324372; Email: li99@bjmu.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Peking University International Hospital
      • Contact: Hui Gao, Doctor; Phone Number: 8613811833264; Email: gh841017@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Idiopathic retroperitoneal fibrosis diagnosed on CT or MRI. For patients with suspected secondary retroperitoneal fibrosis or atypical idiopathic retroperitoneal fibrosis suggested by imaging, idiopathic retroperitoneal fibrosis should be confirmed by puncture biopsy
2. Increased ESR and CRP levels caused by this disease and/or active lesions suggested on imaging

Exclusion Criteria:

1. Secondary retroperitoneal fibrosis
2. Having used corticosteroid (equivalent to >10 mg per day of prednisone), immunosuppressant, or biologic within 3 months prior to enrollment
3. Having any contraindication of prednisone or sirolimus, or allergy to sirolimus, or having experienced serious adverse reactions from the previous use of any of the above drugs
4. Massive proteinuria (24-hour urine protein quantitation ≥3 g), moderate-to-severe anemia (hemoglobin <90 g/L), agranulocytosis (white blood cell count <1.5×10^9/L or neutrophil count <0.5×10^9/L), platelet count <50×10^9/L, interstitial pneumonia
5. Uncontrollable diabetes, hypertension, hyperlipidemia, infection, or heart failure, or other serious complications
6. Malignancy
7. Pregnancy or need for pregnancy in the near future
8. Unable to adhere to follow-up or refuses to provide consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sirolimus group; Sirolimus: 2 mg/day for the first 3 days and 1 mg/day thereafter. The plasma drug concentration was monitored at 14 days, 12 weeks, and 48 weeks of medication to maintain a plasma drug concentration of 4-15 ug/L. Prednisone: 0.8 mg/kg/d (maximum dose: 60 mg/d), reduced by 5 mg every 14 days, by 2.5 mg every 2 weeks after 30 mg/d until discontinuation.	Drug: Sirolimus; The efficacy is evaluated at 12 weeks, and treatment will be adjusted according to the control of disease and adverse effects.For experimental group, if a patient is assessed as treatment failure (TS), the patient should be withdrawn from the study and receive rescue treatment. Whereas, a patient would be transferred to the control group if he/ she cann't stand the side effects of sirolimus but not serious adverse event (SAE).; Drug: Corticosteroid; The efficacy is evaluated at 12 weeks, and treatment will be adjusted according to the control of disease and adverse effects. For active comparator group, if a patient is assessed as treatment failure (TF), the patient should be withdrawn from the study and receive rescue treatment.; Other Names: Prednisone
Active Comparator: corticosteroid group; Prednisone: 0.8 mg/kg/d (maximum dose: 60 mg/d), reduced by 5 mg every 14 days, by 2.5 mg every 2 weeks after 30 mg/d until 5-7.5 mg/d.	Drug: Corticosteroid; The efficacy is evaluated at 12 weeks, and treatment will be adjusted according to the control of disease and adverse effects. For active comparator group, if a patient is assessed as treatment failure (TF), the patient should be withdrawn from the study and receive rescue treatment.; Other Names: Prednisone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recurrence rate	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Treatment failure rate	12 weeks of treatment
Cumulative dose of prednisone	48 weeks
Size of retroperitoneal fibrotic mass	48 weeks

Collaborators and Investigators

• Sponsor: Peking University International Hospital
• Investigators: Principal Investigator: Hui Gao, Doctor, Peking University International Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 25, 2019
• First Submitted That Met QC Criteria: August 5, 2019
• First Posted (Actual): August 6, 2019

Study Record Updates

• Last Update Posted (Actual): June 4, 2025
• Last Update Submitted That Met QC Criteria: June 1, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Sirolimus; mTOR inhibitor; Retroperitoneal Fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Retroperitoneal Fibrosis; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Sirolimus; Prednisone
• Other Study ID Numbers: Sirolimus for RPF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No