Treatment of Macrophage Activation Syndrome (MAS) With Anakinra (MAS)
|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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02780583|
Recruitment Status : Recruiting
First Posted : May 23, 2016
Last Update Posted : January 23, 2018
|Condition or disease||Intervention/treatment||Phase|
|Macrophage Activation Syndrome||Drug: kineret Drug: placebo||Phase 1|
Macrophage activation syndrome (MAS) is a disorder whereby the immune system generates very high levels of substances (cytokines) that promote inflammation to the extent dysfunction occurs in multiple organ systems which if unchecked, is frequently fatal to the affected individual. This can occur in the setting of a number of different immune system disorders including, systemic lupus, systemic-onset juvenile arthritis, and adult-onset Still's disease. MAS can also occur in response to infection with certain viruses such as Epstein-Barr virus (EBV) and malignancies involving lymphocytes.
Because of the high fatality of MAS (>50%), a number of different treatments have been tried to manage this disorder, including use of high-dose steroids, immune suppressants such as cyclosporine, and cytotoxic chemotherapy treatments (etoposide) with variable success and/or severe complications of immune suppression (as may occur with etoposide). A number of recent case reports and case series have reported success using cytokine-blocking therapies such as anakinra in the treatment of MAS that is associated with systemic-onset juvenile idiopathic arthritis and adult Still's disease. Anakinra is a bio-engineered form of the naturally occurring interleukin-1 receptor antagonist (IL-1ra), that blocks the action of interleukin-1, one of the cytokines that is expressed and present in very high amounts in patients who have MAS. Anakinra/Il-1ra is an attractive treatment for patients presenting with clinical features of MAS because it has a relatively short half-life and is easy to administer by subcutaneous injection. In previous trials of its use in patients with clinical features of bacterial sepsis (fever, elevated heart rate, low/falling blood pressure) , it was shown that anakinra does not have a harmful effect but also did not appear to have any benefit with repect to the defined primary outcome of improved survival. However, a recent re-analysis of the data accumulated in these same previous sepsis trials (for which the primary defined outcome was survival) indicates that survival was actually increased in the subgroup of sepsis patients with features of MAS (ferritin elevations in excess of 2,000 ng/ml, signs of coagulopathy, and liver enzyme elevations) who were randomized to receive anakinra compared to the subgroup of sepsis patients with features of MAS who were randomized to receive placebo.
Previous doses of anakinra up to 3500 mg/day over 72 hours that were employed in the trials of adult patients with sepsis were noted to be well tolerated without increased adverse outcomes compared to patients randomized to placebo. Recent case reports have shown that doses up to 100 mg every 6 hours were efficacious and well tolerated in children with systemic onset juvenile arthritis complicated by refractory macrophage activation syndrome.
This study will be the first controlled study to confirm whether anakinra at dose of 10 mg/kg/day to a maximum of dose of 200 mg/day divided every 12 hours (for children ≤40 kg) or 5 mg/kg/day up to a maximum dose of 400 mg/day divided every 6 hours (children > 40 kg and adults) does not result in increased mortality or infection complications when administered in addition to current UAB standard of care treatment (corticosteroids) to children and adults hospitalized with suspected macrophage activation syndrome.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Randomized Placebo Controlled Trial of Subcutaneous rhIL-1A (Anakinra) in the Management of Hospitalized Pediatric and Adult Patients With Macrophage Activation Syndrome|
|Study Start Date :||May 2016|
|Estimated Primary Completion Date :||June 2019|
|Estimated Study Completion Date :||October 2019|
Placebo Comparator: placebo
methylprednisolone intravenously, placebo shots every 6 hours
placebo injection administered every 6 hours along with intravenous methylprednisolone
Other Name: normal saline
Experimental: anakinra (Kineret)
methylprednisolone intravenously, anakinra shots every 6 hours
anakinra administered subcutaneously every 6 hours x 72 hours along with intravenous methylprednisolone
Other Name: Anakinra
- Number of acquired infections, deaths in treatment group vs placebo group [ Time Frame: within 72 hours after baseline ]The primary outcome measure is to determine whether hospital acquired infections or deaths are increased when anakinra is added to corticosteroid use during the first 72 hours of MAS management
- Normalization of elevations of MAS activity markers in treatment group vs placebo group [ Time Frame: baseline to 72 hours after baseline ]Another purpose of this study is to determine whether adding anakinra to corticosteroids in the first 72 hours of MAS treatment results in greater normalization of MAS activity markers including serum ferritin, CRP, LDH, d-dimer/fibrinogen
- Total corticosteroid use and chemotherapy rescue treatment in anakinra treated group vs placebo treated group [ Time Frame: 2 years post enrollment ]Determine if treatment anakinra decreases the overall doses of steroids required to effectively manage anakinra, and if treatment with anakinra decreases the need to use chemotherapy drugs (etoposide) to treat MAS.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02780583
|Contact: Walter W Chatham, MD||(205) firstname.lastname@example.org|
|Contact: Angela C Kendrach, RN||(205)-975-8091 ext email@example.com|
|United States, Alabama|
|University of Alabama at Birmingham||Recruiting|
|Birmingham, Alabama, United States, 35294|
|Principal Investigator:||Walter W Chatham, MD||University of Alabama Hospital|
|Principal Investigator:||Randall Q Cron, MD||Children's Hospital of Alabama|