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Study of Sirolimus in Idiopathic Retroperitoneal Fibrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04047576
Recruitment Status : Recruiting
First Posted : August 6, 2019
Last Update Posted : December 8, 2022
Sponsor:
Information provided by (Responsible Party):
Gao Hui, Peking University International Hospital

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Retroperitoneal Fibrosis Drug: Sirolimus Drug: Corticosteroid Phase 2 Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Study of Prednisone Versus Sirolimus in the Treatment of Idiopathic Retroperitoneal Fibrosis
Actual Study Start Date : July 1, 2018
Estimated Primary Completion Date : July 2025
Estimated Study Completion Date : July 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids

Arms and Interventions
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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 Name: 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 Name: Prednisone


Outcome Measures
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Primary Outcome Measures :
  1. Recurrence rate [ Time Frame: through study completion, an average of 1 year ]

Secondary Outcome Measures :
  1. Treatment failure rate [ Time Frame: 12 weeks of treatment ]
  2. Cumulative dose of prednisone [ Time Frame: 48 weeks ]
  3. Size of retroperitoneal fibrotic mass [ Time Frame: 48 weeks ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04047576


Contacts
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Contact: Hui Gao, Doctor 8613811833264 gh841017@126.com
Contact: Zhan-guo Li, Professor 8610-88324372 li99@bjmu.edu.cn

Locations
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China, Beijing
Peking University International Hospital Recruiting
Beijing, Beijing, China, 100000
Contact: Hui Gao, Doctor    8613811833264    gh841017@126.com   
Sponsors and Collaborators
Peking University International Hospital
Investigators
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Principal Investigator: Hui Gao, Doctor Peking University International Hospital
More Information
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Responsible Party: Gao Hui, Principal Investigator, Peking University International Hospital
ClinicalTrials.gov Identifier: NCT04047576    
Other Study ID Numbers: Sirolimus for RPF
First Posted: August 6, 2019    Key Record Dates
Last Update Posted: December 8, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Gao Hui, Peking University International Hospital:
mTOR inhibitor
Sirolimus
Retroperitoneal Fibrosis
Additional relevant MeSH terms:
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Fibrosis
Retroperitoneal Fibrosis
Pathologic Processes
Sirolimus
Prednisone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
 Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors