The primary objective of the study is to demonstrate that patients with very early arthritis have a higher probability of achieving a state of clinical remission at end of infliximab therapy if treated with infliximab plus MTX when compared to MTX…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Comparison of presence of clinical remission between treatment with infliximab
plus MTX versus MTX monotherapy and supportive treatment only at end of
infliximab therapy, i.e. at at least 2 consecutive visits after month 3 during
the first 54 weeks.
Secondary outcome
Comparison, Group I versus Group II and Group III of:
* the presence of persistent clinical remission at week 106;
* the presence of persistent clinical remission at week 54 since start of
therapy;
* the presence of persistent clinical remission at week 106;
* radiographic progression at week 22, 54 and 106;
* the presence of clinical remission at every time point during the trial;
* the presence of clinical remission by SDAI and CDAI at every time point
during the trial;
* the presence of remission by Pinals criteria at every time point during the
trial
* the presence of near-remission (DAS28 < 2.6) at every time point during the
trial;
* the duration of clinical remission or near-clinical remission during the
entire trial;
* time to remission;
* time to relapse after withdrawal of infliximab therapy in patients who
achieved persistent clinical remission;
* all variables included in the WHO/ILAR core set for clinical trials
(66-joints swollen joint count, 68-joints tender joint count, pain, patient and
evaluator global assessments, health assessment questionnaire (HAQ), CRP, ESR)
at every time point during the trial;
* DAS28, SDAI, CDAI and RADAI at every time point during the trial;
* ACR 50 and 70 response, SF36, Fatigue (VAS) and Pharmacoeconomics at week 2,
6, 14, 22, 30, 38, 54, 70 and 106;
* glucocorticoid and NSAID/coxib dosage at every time point during the trial;
* number of visits at which relapse from remission was noted.
Background summary
The chronic erosive arthritides, among which rheumatoid arthritis (RA) is the
most common disease, are characterized by inflammation of joints, tendons and
tendon sheaths. In order to suppress the inflammatory activity and to retard or
even stop the joint damage, disease modifying antirheumatic drugs (DMARDs) are
used to treat patients with RA. Long-term clinical remission seems to be
pivotal to stop the pathophysiological process underlying progressive joint
damage. Very early arthritis may be a manifestation of a spectrum of different
diseases, with a heterogeneous outcome, but arthritis persistent for >12 weeks
was prone to become RA.
To understand early arthritis and develop new treatment approaches, a number of
investigators have both established early arthritis clinics (EAC) and conducted
treatment trials which differ in the criteria for patients to be included, such
as whether the patient had to fulfill classification criteria. However, there
is a strong belief that starting treatment before patients fulfill the
classification criteria for RA may be beneficial. If the goal is to prevent the
evolution to RA in patients with very early inflammatory arthritis or prevent
progressive inflammatory disease in all patients, it is essential to begin
therapy early in the course and regardless of disease designation.
The primary hypothesis is that the development of persistent chronic arthritis
(e.g. RA) can be prevented (durable state of remission, or even cure) if highly
effective therapy (Infliximab plus MTX as compared to symptomatic therapy) is
started during the earliest clinically perceptible phase of the disease shortly
after the first signs of persistent arthritis.
Study objective
The primary objective of the study is to demonstrate that patients with very
early arthritis have a higher probability of achieving a state of clinical
remission at end of infliximab therapy if treated with infliximab plus MTX when
compared to MTX monotherapy or supportive treatment only.
Study design
This is a double blind, randomized, placebo controlled, multi-center trial in
200 subjects
Intervention
200 subjects (80 per DMARD treatment arm and 40 in the supportive treatment
arm) will be randomly assigned, stratified by glucocorticoid use to one of the
following treatment groups:
Group I To receive symptomatic therapy as well as oral methotrexate and
infliximab
Group II To receive symptomatic therapy as well as oral methotrexate and
placebo infusions.
Group III To receive symptomatic therapy as well as placebo tablets and
placebo infusions
Symptomatic therapy will consist of NSAIDs (or coxib) and, if deemed indicated,
glucocorticoids at a dose of no more than 10mg/day of prednisone or equivalent
dose (no MTX or other DMARDs). In addition, patients will receive proton pump
inhibitors for gastric protection.
Total weekly dose for MTX or placebo tablets will be standardized throughout
the protocol. MTX will be dosed orally, according to a rapid dose escalation
scheme, as used previously in several clinical trials in early RA. In brief,
MTX will be started at 10 mg/week, and increased to 25 mg/week in three steps
with a 2 weeks interval, unless toxicity prevents such a strategy. If the
patient goes into remission during the dose escalation period, escalation
should be halted and the dose should be kept stable until patient is a primary
success and until end of study treatments at week 54 (see section 9.4 for
definition of remission). If remission is not sustained, dose escalation will
be resumed.
Infliximab will be administered by intravenous infusions at a dose of 3 mg/kg
at 0, 2 and 6 weeks, and at 5 mg/kg every 8 weeks thereafter.
To reduce MTX-related adverse events, all patients will receive folate
supplementations (5mg/day on 2 days per week).
Study burden and risks
There are 18 visit during 2 years of study, blood is taken on every studyvisit.
The time between 2 visits varies from 4 to 8 weeks. Each patient is treated
with infliximab-placeboinfusions in week 1,2 and 6 of the study and after that
every 8 weeks (max 9 infusions). A studyvisit will take 1 hour time and about 4
hours for a visit with an infusion of infliximab/placebo.
Possible risks to the patient are mainly associated with the toxicity of the
drugs used in this study:
Infliximab:
-increased risk for tuberculosis and reactivation of hepatitis infection
-increased risk for infections
-skinrash
-changes in bloodpressure during infusion
More general adverse events:
-nausea, vomiting, stomache ache
-blood: decrease in leocicytes
-liver- and kidney function disturbance
Drawing blood and the infusions administered within the context of this
clinical trial can lead to light pain and hemorrhages at the administration
site.
The amount of radiation the patient will receive for the radiograph of the
chest and for the hand and foot is within the recommended limits. The risk
brought by these examinations can be classified as minimum.
Albinusdreef 2
2333 ZA Leiden
NL
Albinusdreef 2
2333 ZA Leiden
NL
Listed location countries
Age
Inclusion criteria
1) Men and women, >= 18 and <= 75 years of age
2) The presence of arthritis:
a) Must be established in a rheumatology center,
b) Must be present in at least 2 joints of the 66 joint count
c) Without any previous episodes of inflammatory joint disease
3) Duration of symptoms :
a) Must be 2 weeks at least
b) Must be 16 weeks at most
Exclusion criteria
*previous treatment with corticoseroids or DMARD's
*positive tuberculosis test
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-002787-26-NL |
| CCMO | NL19673.058.07 |
| Other | volgt |