IPF
Conditions
Interventions
Intavenous administration of infliximab (chimeric monoclonal anti-TNF-alpha
5 mg/kg) vs placebo (2:1) next to standard treatment with prednsiolone and azathioprine
given at week
0,2,6,12,18,24,30,36,42, and 48.
Sponsors
Investigator's initiated study performed by BENEFIT study group
Eligibility
Inclusion criteria
Inclusion criteria: 1. Diagnosis of IPF(2): a) If possible a thoracoscopic or open lung biopsy showing UIP. A thoracoscopic or open lung biopsy must be performed in patients 50 years fulfilling all above mentioned criteria a BAL to exclude other causes of interstitial lung disease is sufficient and a lung biopsy is not necessary. 2. Show stable disease or failure to respond to standard medication (i.e. azathioprine and prednisolone) (as defined by the ATS/ERS criteria(2)) during a minimum of 3 months prior to the study, with a minimum dose of prednisolone (or equivalent) of 20 mg daily, and azathioprine 2 mg per kg with a maximum of 200 mg daily during 3 months. 3. Men and women between 40 and up until 79 years. 4. Diagnosis of IPF within the past 36 months 5. Men and women must use adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) for the duration of the study and should continue such precautions for 6 months after receiving the last infusion. 6. The screening laboratory test results must meet the following criteria: a. Haemoglobin > 8.5 g/dL (5.3 mmol/L) b. WBC > 3.5 x 109/L c. Neutrophils > 1.5 x 109/L d. Platelets > 100 x 1012/L e. SGOT (AST) and alkaline phosphatase levels must be within 3 times the upper limit of normal range for the laboratory conducting the test. 7. Patient must be able to adhere to the study visit schedule and other protocol requirements. 8. Patient must be able to communicate meaningfully with the study personnel. 9. The patient must be capable of giving informed consent and the consent must be obtained prior to any screening procedures. 10. Must have a chest radiograph within 3 months prior to first infusion with no evidence of malignancy or infection. 11. Are considered eligible according to the tuberculosis (TB) eligibility assessment, screening, and early detection of reactivation rules defined in Section 4.3
Exclusion criteria
Exclusion criteria: 1. Critical low lung function: FVC 40 mmHg at rest. 17. Presence of a transplanted organ (with the exception of a corneal transplant > 3 months prior to screening). 18. Malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence). 19. History of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly. 20. Known recent substance abuse (drug or alcohol). 21. Poor tolerability of venipuncture or lack of adequate venous access for required blood sampling during the study period. 22. Have a chest radiograph at screening that shows evidence of malignancy, infection, or any abnormalities suggestive of TB as described in Section 4.3.2.1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in FVC from baseline Time to disease progression (ATS criteria) | — |
Secondary
| Measure | Time frame |
|---|---|
| Cytokines -BAL: pro-inflammatory and pro-fibrotic cytokines; growth factors; MMP's; surface (activation) markers on resident cells - Serum:pro-inflammatory and pro-fibrotic cytokines; growth factors; MMP's; surface markers on resident cells - Blood: surface (activation) markers on white blood cells Clinical secondary endpoints - Six minute walk distance (6-MWD) - Borg dyspnea score after 6-MWT - Difference in O2 saturation and heart rate before and after 6-MWT - PO2 and p(A-a)O2 at rest and room air - HRCT: fibrosis and groundglass Lung function (FVC,TLC,RV,DLco) | — |
Contacts
Public ContactPaul Bresser
Department of Pulmonology; F5-144
Outcome results
None listed