|- candidate number||1743|
|- NTR Number||NTR449|
|- Date ISRCTN created||27-jan-2006|
|- date ISRCTN requested||18-nov-2005|
|- Date Registered NTR||4-okt-2005|
|- Secondary IDs||N/A |
|- Public Title||Anti-TNF-alpha (Infliximab) in Complex Regional Pain Syndrome.|
|- Scientific Title||A double blind, randomized, placebo controlled trial of anti-TNF-alpha chimeric monoclonal antibody (Infliximab, Remicade) in complex regional pain syndrome type 1.|
|- ACRONYM||InCRePaS study|
|- hypothesis||Infliximab counteracts the increased synthesis of tumor necrosis factor alpha (TNF-alpha), after which inflammation will decrease and recovery of the disease occur.|
|- Healt Condition(s) or Problem(s) studied||Complex regional pain syndrome type 1 (CRPS I)|
|- Inclusion criteria||Men and women between 18 and up until 65 years. Established diagnosis of CRPS-1 according to the Bruehl / Budapest criteria.|
Are considered eligible according to tuberculosis screening criteria.
|- Exclusion criteria||1. Disease related reasons;|
2. Abnormal laboratory findings;
3. Adverse co-medication (such as corticosteroids, NSAIDs);
4. In general: concomitant congestiv heart failure, pregnancy, receiving other recombinat products, history of serious infections, HIV, hepatitis B or C, abnormal chest radiograph, history of lymphoproliferative disease, opportunistic infection (e.g. herpes zoster), presence of a transplanted solid organ, history of alcohol abuse.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-nov-2005|
|- planned closingdate||31-dec-2007|
|- Target number of participants||24|
|- Interventions||Subjects are assigned to receive either intraveneous Infliximab (5mg/kg) or placebo 3 times in 6 weeks.|
|- Primary outcome||Reduction in clinical signs of regional inflammation.|
|- Secondary outcome||Improvement in subjective scores of quality of life. Normalization of levels of inflammatory mediators in fluid of induced blisters.|
|- Trial web site||N/A|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||Dr. F.J. Zijlstra|
|- CONTACT for SCIENTIFIC QUERIES||Dr. F.J. Zijlstra|
|- Sponsor/Initiator ||Erasmus Medical Center, Department of Anesthesiology|
(Source(s) of Monetary or Material Support)
|Ministry of Economic Affairs, Centocor BV Leiden|
|- Publications||Summary – conclusions:|
There were problems with the patient inclusion from the start of the study due to several factors. Eventually only 13 patients could be included before the end of the study period, and all were analyzed: 7 in the intervention group and 6 in the placebo group.
Despite the very small study we found an effect on inflammatory mediators, especially TNFα, and on quality of life, but not on other secondary parameters.
One serious adverse event was reported in the placebo group of this trial. The relationship to the treatment was classified as ‘other’. In the intervention group no serious adverse events were reported.
The registration of the adverse advents shows 28 adverse events in the infliximab group, compared to 51 in the placebo group. Only in 2 cases (one with a transitory increased blood pressure, and one with constipation), this was ‘probably’ related to infliximab.
Although the study was very small, and the patients were carefully selected, this indicates that infliximab is a safe treatment for patients with regional inflammation in the acute stage of CRPS.
In spite of the small number of participants a promising trend towards an effect of infliximab on the initially high TNFα concentration, as well as on the quality of life in patients with a neuroinflammation in acute CRPS has been found. Unfortunately this study has been terminated before the required number of participants for sufficient power was reached, so we cannot draw any definitive conclusions.
Therefore, a follow-up study into the effect of Remicade on the clinical signs of inflammation in CRPS with more participants is recommended.
|- Brief summary||In most cases, adequate pharmacotherapeutic treatment of patients with complex regional pain syndrome type 1 (CRPS1, formerly indicated as post-traumatic dystrophy) in an extremity is not available. Some pain relief could be obtained, but recovery of the neuro-inflammatory signs of the disease is barely achieved. Chronic CRPS 1 could even lead to amputation of the dystrophic hand or toot. Usually this is a direct effect of unbearable continuous pain and disuse of the extremity. Evidence has been found that in the initial stage of the disease inflammatory processes play an important role. The marked elevated levels of pro-inflammatory cytokines, such as TNFá, lead to the conclusion that anti- TNF could be beneficial in the treatment of CRPS1. In two patients with active inflammatory signs during CRPS1, the effects of anti-TNF (infliximab) has been shown promising. Therefore, in some patients this new approach could attribute to the recovery and prevent further development of a chronic disease.In this randomised controlled trial, monitoring of the patients during the treatment will be achieved by means of computer assisted videothermography, parameters for pain intensity, mobility and quality of life. Furthermore, blood samples and blister fluid from both the involved and uninvolved extremity will be subjected to measurements of biochemical mediators. These data will provide detailed information of inflammatory changes in relation to the experience of pain and immobility. Treatment by infliximab could provide more insight in the complex mechanisms underlying this invalidating chronic disease.|
|- Main changes (audit trail)|
|- RECORD||4-okt-2005 - 26-nov-2010|