Cyclophosphamide Systemic Sclerosis Associated Interstitial Lung Disease

NCT01570764 | Completed Phase 3 DMC

• 2 other identifiers: P0812412011-004709-26
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

By including in this study patients with significant worsening of their lung volumes and / or their DLCO (carbon monoxide diffusing capacity) in the previous year, on the basis of an open retrospective study we recently conducted, we hope to demonstrate that a strategy combining prednisone and intravenous cyclophosphamide therapy is accompanied by an increase in the frequency stabilization / improvement of lung volumes and / or DLCO of patients at 12 months of 15% in the placebo and prednisone cyclophosphamide 50% in cyclophosphamide and prednisone.We also hope to demonstrate significant decrease in the number of patients excluded for failure in the CYC arm as compared to the placebo arm.

Conditions

Systemic Sclerosis; Scleroderma; Interstitial Lung Disease; Lung Fibrosis

Keywords

Systemic sclerosis; Interstitial lung disease; Worsening; Cyclophosphamide; Intravenous

Outcome Measures

Primary Outcomes (1)

• Forced vital capacity

  Forced vital capacity at 12 months

  at 12 months

Secondary Outcomes (9)

• Mortality

  at 12 months

• Progression free survival

  at 12 months

• Carbon monoxide diffusing capacity (DLCO)

  at 12 months

• Treatment failure

  at 12 months

• Walk test distance

  at 12 months

Study Arms (2)

Cyclophosphamide

EXPERIMENTAL

Prednisone 15 mg/d + monthly pulse cyclophosphamide 700 mg/m ² diminished to 600 mg/m ² in patients over 65 years or having a creatinine clearance lower than 30 ml/min for 12 months.

Drug: Cyclophosphamide

Placebo

PLACEBO COMPARATOR

Prednisone 15 mg/d + monthly pulse of placebo of cyclophosphamide. The posology and the methods of administration of the placebo of cyclophosphamide (NaCl) will be the same as those used for cyclophosphamide

Drug: Placebo

Interventions

Cyclophosphamide DRUG

Prednisone 15 mg/d + monthly pulse cyclophosphamide 700 mg/m ² diminished to 600 mg/m ² in patients over 65 years or having a creatinine clearance lower than 30 ml/min for 12 months.

Cyclophosphamide

Placebo DRUG

Prednisone 15 mg/d + monthly pulse of placebo of cyclophosphamide. The posology and the methods of administration of the placebo of cyclophosphamide (NaCl) will be the same as those used for cyclophosphamide

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old
• Signed informed consent
• Smokers may be included (DLCO must be performed at least 72h after stopping tobacco intake).
• Patients with pulmonary hypertension (mean pulmonary arterial pressure \<35 mmHg upon right heart catheterisation) secondary to hypoxia due to pulmonary fibrosis will also be included into the study.
• : Contraception considered effective by the investigator (abstinence and / or oral contraception or mechanical) for women of childbearing age (negative pregnancy test at baseline)
• Affiliation with a mode of social security (profit or being entitled)

You may not qualify if:

• Prednisone prescribed a dose greater than 15 mg/d during the last 3 months.
• Left ventricular ejection fraction below 40% evaluated by echocardiography.
• Out of proportion pulmonary hypertension (mean pulmonary artery pressure above 35 mmHg upon right heart catheterization).
• CYC treatment during the last 12 months.
• Allergy, hypersensitivity or documented adverse events or contra-indications to the drugs used in the study (cyclophosphamide, Uromitexan, corticosteroids, domperidone ...)
• Severe infection: sepsis, cellulitis, gangrene in the last three months
• Past history of cystitis related to cyclophosphamide treatment
• Association to another connective disease : systemic lupus erythematosus, syndrome of Gougerot-Sjögren with anti-SSA/SSB, mixed connective tissue disease
• Patient breastfeeding
• Failure to sign the informed consent or unable to consent
• Patient participating in another clinical trial

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Hôpital Claude-Huriez: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Cochin Hospital

Paris, 75014, France

Location

MeSH Terms

Conditions

Scleroderma, Systemic; Scleroderma, Diffuse; Lung Diseases, Interstitial; Pulmonary Fibrosis

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Lung Diseases; Respiratory Tract Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Luc Mouthon, MD, PhD

  Cochin Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2012
• First Posted: April 4, 2012
• Study Start: January 14, 2013
• Primary Completion: February 22, 2018
• Study Completion: February 22, 2018
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)