Anti-Cytokine Therapy for Hemodialysis InflammatION
Condition: End-Stage Renal Disease
MeSH terms: Kidney Failure, Chronic; Inflammation
Intervention: Anakinra; Placebo
Intervention description: Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1α and IL-1β by competitively binding to the interleukin-1 type I receptor (IL-1RI). It is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra) but differs from human IL-1Ra in that it has the addition of a single methionine residue at the amino terminus. It is supplied commercially in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe contains: 0.67 ml (100 mg) of anakinra in a solution (pH 6.5) containing sodium citrate (1.29 mg), sodium chloride (5.48 mg), disodium EDTA (0.12 mg) and polysorbate 80 (0.70 mg) in Water for Injection, USP.; Saline (0.9%) will be used as the placebo, in single use 1 ml prefilled glass syringes as a sterile, clear, colorless-to-white, preservative free solution.
Intervention MeSH terms: Interleukin 1 Receptor Antagonist Protein
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: ESRD; End-Stage Kidney Disease

Summary:

      Anti-Cytokine Therapy for Hemodialysis InflammatION (ACTION) is a phase II multi-center study
      to evaluate the safety and tolerability of anakinra, an IL-1 receptor antagonist, for
      patients treated with maintenance hemodialysis.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Maintenance hemodialysis therapy 3 times per week for end-stage renal disease

          2. ≥6 months since hemodialysis initiation

          3. C-reactive protein measured by high sensitivity assay (hsCRP) ≥2.0 mg/L at screening
             and within 10 days prior to randomization

          4. Most recent single pool Kt/V > or = 1.2 within 30 days prior to first screening visit

          5. Negative tuberculosis interferon gamma release assay (e.g. Quantiferon-TB Gold) for
             tuberculosis unless documented treatment for a) positive PPD, b) positive interferon
             gamma release assay, or c) tuberculosis.

          6. Negative human immunodeficiency virus (HIV) antibody test, negative hepatitis C Ab
             test unless viral clearance following direct antiviral therapy is documented, and
             negative hepatitis B surface antigen positivity.

          7. For women of childbearing potential, willingness to use a highly effective method of
             birth control for up to 4 weeks after the last dose of anakinra.

          8. Ability to provide informed consent

        Exclusion Criteria:

          1. Current or anticipated use of a hemodialysis central venous catheter

          2. Acute bacterial infection, including vascular access infection, within 60 days prior
             to screening unless treated with antibiotics and resolved. Any chronic bacterial
             infection (e.g., osteomyelitis or bronchiectasis)

          3. Hospitalization within 30 days unless for vascular access procedure

          4. Cirrhosis

          5. Malignancy within the past 5 years with exception of basal or squamous cell carcinoma

          6. Use of an immunosuppressive drug within the past 3 months except low doses of oral
             corticosteroids (total daily dose ≤10 mg/day of prednisone or equivalent)

          7. Receipt of live vaccine within the past 3 months. Live vaccines include Varicella
             zoster, measles, oral polio, rotavirus, yellow fever, and the nasal spray influenza
             vaccine

          8. Absolute neutrophil count (ANC) <2,500 cells/mm3 (2.5 x 109 cells/L)

          9. Platelet count <100,000/mm3 (100 x 109/L)

         10. Known allergy to anakinra

         11. Anticipated kidney transplantation, change to peritoneal dialysis, or transfer to
             another dialysis unit within 9 months

         12. Expected survival less than 9 months

         13. Pregnancy, anticipated pregnancy, or breastfeeding

         14. Incarceration

         15. Receipt of an investigational drug within the past 30 days

         16. Current or anticipated participation in another intervention study