Anti-Cytokine Therapy for Hemodialysis InflammatION

Browse trials for

• Kidney Failure, Chronic 2,085
• Inflammation 3,439

Keywords

• ESRD
• End-Stage Kidney Disease

Kidney Failure, Chronic

2,085 studies on the registry are indexed under Kidney Failure, Chronic; 260 are open to participants now.

This study's enrollment of 80 is above the median of 55 across 1,557 interventional studies indexed under Kidney Failure, Chronic.

Lead sponsor

University of Pennsylvania is the lead sponsor of 1,635 studies on the registry; 239 are open to participants now.

Of its 154 completed or terminated interventional studies of FDA-regulated products, 104 (68%) have results posted.

Study arms

• Active comparator
  Anakinra

  Anakinra (Kineret®) is a therapeutic agent that blocks the effects of IL-1 alpha and IL-1 beta by competitively binding to the interleukin-1 type I receptor (IL-1RI). Anakinra is a recombinant, non-glycosylated form of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). Anakinra will be supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution. Each syringe will contain 100 mg in 0.67 ml solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), sodium citrate (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP.

  Drug: Anakinra

• Placebo comparator
  Placebo

  Saline (0.9%) will be used as the placebo, supplied in pre-filled syringes as a sterile, clear, colorless-to-white, preservative free solution.

  Drug: Placebo

Interventions

• DrugAnakinra

  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.

  Also known as: Kineret®

• DrugPlacebo

  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

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

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

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

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

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

Secondary outcomes

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

   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.

   Time frame: 24-week treatment period

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

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

   Time frame: change after 24 weeks 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

    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.

    Time frame: 24 Weeks (end of treatment phase)

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

    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.

    Time frame: 24 Weeks (end of treatment phase)

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

    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.

    Time frame: Change after 24 weeks of treatment

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

    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.

    Time frame: Change after 24 weeks of treatment

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

    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.

    Time frame: 24 Weeks (end of treatment phase)

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

    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.

    Time frame: 24 Weeks (end of treatment phase)

Baseline characteristics

Study documents

• Protocol and statistical analysis plan · May 8, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Research results will be made available to the scientific community and public in a timely manner. The primary method by which data will be shared with the scientific community will be through peer-reviewed publications and presentation at scientific and professional society meetings. In addition, data and results will be submitted to the NIH in the annual progress reports required under the terms and conditions of the funding award. This study will also be registered with clinicaltrials.gov before initiation. Data from the study will be submitted to the NIDDK Data Repository in accordance with the NIDDK Data Sharing policy. The policy requires that data sets be transferred no later than 2 years after study completion or 1 year after publication of the primary results, whichever comes first. Through the repository, the study data will be made available to external investigators.