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NCT Number: NCT03141983

Anti-Cytokine Therapy for Hemodialysis InflammatION

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.

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Key information

Conditions

End-stage Renal Disease Chronic Disease Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Kidney Failure, Chronic Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Urogenital Diseases Urologic Diseases

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

The George Washington University, Washington D.C., District of Columbia, United States

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About this study

The ACTION Trial will enroll 80 participants being treated with maintenance hemodialysis for end-stage renal disease. Participants will be randomized to receive Anakinra, 100 mg administered intravenously 3 times per week at the end of the hemodialysis session, or matched placebo. The duration of study drug administration is 24 weeks. There will be an additional 24 weeks of follow-up after study drug administration has been completed.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Maintenance hemodialysis therapy 3 times per week for end-stage renal disease
  • ≥6 months since hemodialysis initiation
  • C-reactive protein measured by high sensitivity assay (hsCRP) ≥2.0 mg/L at screening and within 10 days prior to randomization
  • Most recent single pool Kt/V > or = 1.2 within 30 days prior to first screening visit
  • 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.
  • 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.
  • 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.
  • Ability to provide informed consent

Exclusion criteria

  • Current or anticipated use of a hemodialysis central venous catheter
  • 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)
  • Hospitalization within 30 days unless for vascular access procedure
  • Cirrhosis
  • Malignancy within the past 5 years with exception of basal or squamous cell carcinoma
  • 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)
  • 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
  • Absolute neutrophil count (ANC) <2,500 cells/mm3 (2.5 x 109 cells/L)
  • Platelet count <100,000/mm3 (100 x 109/L)
  • Known allergy to anakinra
  • Anticipated kidney transplantation, change to peritoneal dialysis, or transfer to another dialysis unit within 9 months
  • Expected survival less than 9 months
  • Pregnancy, anticipated pregnancy, or breastfeeding
  • Incarceration
  • Receipt of an investigational drug within the past 30 days
  • Current or anticipated participation in another intervention study

Treatment and study plan

Anakinra

Drug

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.

Other names: Kineret®

Placebo

Drug

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.

Primary outcomes

  1. Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis

    Time frame: 48 Weeks (after the 24-week treatment period and the 24-week post-treatment period)

    The primary safety endpoint is serious adverse events per patient-year.

  2. Change in Log-transformed Circulating CRP Concentration After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis

    Time frame: Change from Baseline to 24 Weeks (end of treatment phase)

    For this outcome, CRP measurements from Baseline and Week 24 were compared.

Secondary outcomes

  1. Number of Participants With Adverse Events That Preclude Further Treatment With the Study Agent

    Time frame: 24-week treatment period

    Adverse events were one measure used to assess safety and tolerability of anakinra, for patients receiving maintenance hemodialysis. This measure assessed the number of participants with adverse events that precluded further treatment with the study agent.

  2. Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Infections

    Time frame: 48 weeks

  3. Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Neutropenia

    Time frame: 48 weeks

  4. Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Thrombocytopenia

    Time frame: 48 weeks

  5. Safety and Tolerability of Anakinra, for Patients Receiving Maintenance Hemodialysis - Systemic Hypersensitivity Reactions

    Time frame: 48 weeks

  6. Change in Markers of Inflammation and Oxidative Stress - IL-1β pg/ml

    Time frame: change after 24 weeks of treatment

    Change in circulating markers of inflammation and oxidative stress between baseline and end of treatment

  7. Change in Markers of Inflammation and Oxidative Stress - IL-6, pg/mL

    Time frame: change after 24 weeks of treatment

  8. Change in Markers of Inflammation and Oxidative Stress - IL-10, pg/mL

    Time frame: change after 24 weeks of treatment

  9. Change in Markers of Inflammation and Oxidative Stress - TNF Alpha, pg/ml

    Time frame: change after 24 weeks of treatment

  10. Change in Markers of Inflammation and Oxidative Stress - Albumin, g/dL

    Time frame: change after 24 weeks of treatment

  11. Change in Patient-reported Indicators of Fatigue After 24 Weeks of Treatment

    Time frame: 24 Weeks (end of treatment phase)

    Change in patient reported outcomes using the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale from Baseline to Week 24.

    To score the FACIT-fatigue, all items are summed to create a single fatigue score with a range from 0 to 52. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatigue.

    All participants were assessed with the same scoring system.

  12. Change in Patient-reported Indicators of Depression After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis

    Time frame: 24 Weeks (end of treatment phase)

    Change in patient reported outcomes using the Beck Depression Inventory - II (BDI-II) scale at baseline, Weeks 12, 24 and 28.

    The instrument uses a 21-item self-report inventory measuring the severity of depression in adolescents and adults.The standard cut-offs are as follows: 0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression. Higher total scores indicate more severe depressive symptoms.

  13. Change in Burden of Patient-reported Symptoms After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis

    Time frame: Change after 24 weeks of treatment

    Mean change in patient reported outcomes using the Dialysis Symptom Index, Burden subscale

    The DSI is a 30-question instrument assessing whether participants report a particular symptom during the past week and the severity of that symptom. Symptom burden is assessed using 30 "yes/no" questions. The scale is a count of the number of "yes" responses. The minimum is 0. The maximum is 30. The mean change in score after 24 weeks of treatment was measured. A lower score is better as a higher score indicates greater symptom burden.

  14. Change in Severity of Patient-reported Symptoms After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis

    Time frame: Change after 24 weeks of treatment

    Change in patient reported outcomes using the Dialysis Symptom Index, Severity subscale

    The DSI severity subscale includes 30-questions assessing whether a symptom is present (previous outcome - burden subscale). The severity of each symptom that was reported as being present was assessed by asking patients to rate the degree to which the symptom was bothersome using a five-point Likert scale (1 = "not at all bothersome" to 5 = "bothers very much"). Higher scores indicating greater symptom severity. The minimum score is 30, the maximum score is 150. The mean change was used to measure this outcome.

  15. Change in Patient-reported Indicators of Quality of Life After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis

    Time frame: 24 Weeks (end of treatment phase)

    Change in patient reported outcomes using the Kidney Disease - Quality of Life subscale of the SF-12 (KDQOL SF-12) at baseline, Weeks 12, 24 and 28.

    A higher score reflects a more favorable health state. The questionnaire consists of 24 questions and the total possible score sum is 0-100. Items in the same scale are averaged to create scale scores.

  16. Change in Measure of Muscle Strength (Hand Grip Strength) After 24 Weeks of Treatment for Patients Receiving Maintenance Hemodialysis

    Time frame: 24 Weeks (end of treatment phase)

    Change in measurement of hand grip strength using a standard dynamometer at baseline, Weeks 12, 24 and 28. This was measured in kg using the dominant hand.

Sponsors and collaborators

Lead sponsor

University of Pennsylvania

Other

Collaborators

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Official study title

Anti-Cytokine Therapy for Hemodialysis InflammatION (ACTION): 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

Acronym: ACTION

Important dates

Study start
2017
Primary completion
2021
Study completion
2021
First posted
May 5, 2017
Registry last updated
Mar 14, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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