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Rituximab in Systemic Sclerosis (RECOVER)

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. Read our disclaimer for details. Identifier: NCT01748084
Recruitment Status : Completed
First Posted : December 12, 2012
Last Update Posted : March 2, 2018
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:
The purpose of this study is to determine whether rituximab is effective in the treatment of articular symptoms that occur in systemic sclerosis related polyarthritis

Condition or disease Intervention/treatment Phase
Systemic Sclerosis Drug: Rituximab Drug: Placebo (NaCl) Phase 2 Phase 3

Detailed Description:

Systemic sclerosis (SSc) is a rare disease, characterized by microvascular and immunological changes promoting extra-cellular matrix synthesis and widespread fibrosis. No treatment has yet proven any ability to alter the disease fibrosing process. Specific auto-antibodies are commonly found in this disease, and B lymphocytes are detected in cutaneous and pulmonary infiltrates. Studies derived from murine models suggest a role for B lymphocyte blocking strategies.

This lead to observational trials of B-cell therapy using rituximab in SSc that provided encouraging results with no particular signal concerning tolerability. These trials included heterogeneous patients with variable disease stages and different involved organs, and were mostly unblinded, which preclude any definitive conclusion. However, they support the continuous development of this therapeutic approach.

Taking up the early phase of the diffuse form of the disease is complicated by its rarity and the heterogeneous progression of its visceral complications. This raises the question of selecting a homogeneous group of patients to evaluate. The most convincing results for the use of rituximab in autoimmune conditions have been found in rheumatoid arthritis. Joint involvement is common in SSc with 75% of patients complaining about joint stiffness and pain, and 30% presenting with synovitis, tenosynovitis, or flexion contractures. No specific treatment has already addressed this issue, and it is generally proposed to use small doses of oral corticosteroids in association with methotrexate, by analogy with rheumatoid arthritis. We propose to evaluate the efficacy and safety of rituximab in SSc patients having active arthritis despite first line treatment. Improving the articular involvement would improve the quality of life f SSc patients and effectiveness of rituximab on skin and lung fibrotic involvements will be assessed as secondary outcomes to estimate the overall effects of this drug on SSc.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Evaluation of Rituximab in Systemic Sclerosis Associated Polyarthritis
Actual Study Start Date : April 9, 2013
Actual Primary Completion Date : April 18, 2016
Actual Study Completion Date : April 18, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Scleroderma
Drug Information available for: Rituximab

Arm Intervention/treatment
Placebo Comparator: NaCl
NaCl 500 ml IV day 1 and day 15 plus 100 mg methylprednisolone
Drug: Placebo (NaCl)
Days 1 and 15, NaCl 500 ml plus 100 mg methylprednisolone

Experimental: Rituximab
Rituximab 1G IV day 1 and day 15 plus 100 mg methylprednisolone
Drug: Rituximab
Days 1 and 15, rituximab 1 gramme plus 100 mg methylprednisolone

Primary Outcome Measures :
  1. Number of tender and swollen joints [ Time Frame: at 6 months ]
    Measured out of 53 joints

Secondary Outcome Measures :
  1. Quality of life: SSc-HAQ [ Time Frame: at 6 and 12 months ]
    Validated scores

  2. Scleroderma [ Time Frame: at 6 and 12 months ]
    modified Rodnan skin score

  3. Lung fibrosis [ Time Frame: at 6 and 12 months ]
    Pulmonary functional tests

  4. Quality of life: SF-36 [ Time Frame: at 6 and 12 months ]
    Validated scores

  5. Quality of life: Duruöz index [ Time Frame: at 6 and 12 months ]
    Validated scores

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Systemic sclerosis fulfilling ACR or LeRoy's criteria
  • Active polyarthritis defined by > 6/53 tender joints and > 4/53 swollen joints
  • Ongoing first line therapy by prednisone (max 10 mg/d) and DMARDS (methotrexate, leflunomide, azathioprine or mycophenolate)
  • Birth control if applicable

Exclusion Criteria:

  • Overlap syndrome defined by clinical symptoms and positive specific auto-antibodies (anti-CCP, anti-SSA, anti-DNA DNA anti-Sm) (Rheumatoid factors and anti-RNP are not exclusion criteria)
  • Past therapy with Rituximab.
  • Severe and uncontrolled disease with renal, liver or haematological (neutropenia < 1500 / mm3) failures, pulmonary (FVC < 50%) or cardiac insufficiencies (LVEF < 50%)
  • Not stable corticosteroid therapy or cyclophosphamide use in the last 6 months
  • Infectious risk : viral infections by B or C hepatitis or HIV, hypogammaglobulinemia (< 6 G/L), opportunistic infection or infection requiring IV antibiotics in the last 3 months.
  • Neoplastic solid tumor in the last 5 years
  • Drug or alcool abuses
  • Receiving patient or having received a biotherapy (anti-TNF, abatacept or tocilizumab) in the last 3 months (possible inclusion beyond 3 months)

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 identifier (NCT number): NCT01748084

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Cochin Hospital
Paris, France, 75014
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
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Principal Investigator: Yannick Allanore, MD, PhD Assistance Publique Hôpitaux de Paris, Université Paris Descartes
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Responsible Party: Assistance Publique - Hôpitaux de Paris Identifier: NCT01748084    
Other Study ID Numbers: P110110
2012-001636-56 ( EudraCT Number )
First Posted: December 12, 2012    Key Record Dates
Last Update Posted: March 2, 2018
Last Verified: February 2018
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Systemic sclerosis
B-cell therapy, Anti-CD20 therapy
Quality of life
Lung fibrosis
Randomised controled trial
Additional relevant MeSH terms:
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Scleroderma, Systemic
Scleroderma, Diffuse
Pathologic Processes
Connective Tissue Diseases
Skin Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents