The Effects of Interferon-gamma on Sepsis-induced Immunoparalysis

• Status: Completed
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary aim of this study is to assess the effects of adjunctive therapy with Interferon (IFN)-gamma on immune function in patients with septic shock in a placebo-controlled manner. Moreover, the investigators want to evaluate new markers that could be used to identify patients with immunoparalysis, and to monitor the patient's immunological response to IFN-γ. In addition, mechanistic studies will be performed to further elucidate mechanisms (such as epigenetic modifications) behind immunoparalysis and the effects of IFN-γ on these mechanisms. With use of the results the investigators will obtain in this pilot study, the investigators will conduct a large multicentre clinical trial with IFN-γ.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Radboud University
• Treatments: Interferon-gamma; Interferons

Criteria

Inclusion criteria:

• Written informed consent from patient of legal representative

• Age >18 years

• Presence of septic shock of bacterial origin with evidence of bacterial infection (last 96 hours, with at least one pathogenic microorganism in blood, sputum, urine, normally sterile body fluid, or on central venous catheter; Focus of infection identified (e.g. ruptured bowel, purulent drainage/sputum); or leukocytes in normally sterile body fluid), Two SIRS criteria (last 24 hours, fever (>38.3 ˚C), hypothermia (<35.6 ˚C), tachycardia (>90bpm), tachypnea (>20/min), or partial pressure of arterial carbon dioxide (PaCO2) <32 mmHg, or mechanical ventilation, leukocytosis (>12,000/μl), leucopenia (<4,0000/μl), or >10% immature forms), and presence of shock with need for vasopressor therapy to maintain systolic blood pressure (SBP) ≥ 90 mmHg.

Exclusion Criteria:

• Pregnancy or lactating

• Subjects with a history of allergy or intolerance to IFN-gamma

• Systemic autoimmune disease, hematologic disease (neoplasma, acute leukemia), transplant patients, or patients on steroid medication receiving a prednisolone equivalent of > 5 mg per day

• Human immunodeficiency virus positivity

• Presence of an advanced directive to withhold or to withdraw life sustaining treatment

• Underlying disease with a prognosis for survival < 3 months, or moribund patient highly likely to die within 24 hours.

• Cardiopulmonary resuscitation (<72 hours) before enrollment

• Acute myocardial infarction or pulmonary embolization (<72 hours)

• Participation in a clinical trial until 30 days prior to inclusion

• Subjects with a history of documented epileptic seizures

• Subjects with severe renal impairment (creatinine clearance less than 30 mL/min)

• Subjects with severe liver failure (impaired synthesis of proteins such as coagulation factors manifested by increased prothrombin time)

• Subjects with an absolute neutrophil count of less than 500/mm3 at study entry