The effects of the drug interferon-gamma on suppression of the immune system in patients with sepsis

Phase 1

• Conditions: Sepsis-induced immunoparalysis (SIRS, Sepsis, Septic shock); MedDRA version: 14.1Level: LLTClassification code 10062357Term: SIRSSystem Organ Class: 10018065 - General disorders and administration site conditions; MedDRA version: 14.1Level: PTClassification code 10061218Term: InflammationSystem Organ Class: 10018065 - General disorders and administration site conditions; MedDRA version: 14.1Level: PTClassification code 10040047Term: SepsisSystem Organ Class: 10021881 - Infections and infestations; MedDRA version: 14.1Level: PTClassification code 10061598Term: ImmunodeficiencySystem Organ Class: 10021428 - Immune system disorders; MedDRA version: 14.1Level: PTClassification code 10040070Term: Septic shockSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2012-002491-14-NL
• Lead Sponsor: Radboud University Nijmegen Medical Centre

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-07-19
• Last Update Posted: 30 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Written informed consent from patient of legal representative
2. Age >18 years
3. Presence of septic shock of bacterial origin (A-C required):
A. Evidence of bacterial infection (last 96 hours), 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
B. Two SIRS criteria (last 24 hours): fever (>38.3 °C), hypothermia (<35.6 °C), tachycardia (>90bpm), tachypnea (>20/min), or PaCO2 <32 mmHg, or mechanical ventilation, leukocytosis (>12,000/µl), leucopenia (<4,0000/µl), or >10% immature forms.
C. Presence of shock with need for vasopressor therapy to maintain SBP = 90 mmHg.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1. Pregnancy or lactating
2. Subjects with a history of allergy or intolerance to IFN-?
3. Systemic autoimmune disease, hematologic disease (neoplasma, acute leukemia), transplant patients, or patients on steroid medication receiving a prednisolon equivalent of > 5 mg per day
4. Human immunodeficiency virus positivity
5. Presence of an advanced directive to withhold or to withdraw life sustaining treatment
6. Underlying disease with a prognosis for survival < 3 months, or moribund patient highly likely to die within 24 hours.
7. Cardiopulmonary resuscitation (<72 hours) before enrolment
8. Acute myocardial infarction or pulmonary embolisation (<72 hours)
9. Participation in a clinical trial until 30 days prior to inclusion
10. Subjects with a history of documented epileptic seizures
11. Subjects with severe renal impairment (creatinine clearance less than 30 mL/min)
12. Subjects with severe liver failure (impaired synthesis of proteins such as coagulation factors manifested by increased prothrombine time)
13. Subjects with an absolute neutrophil count of less than 500/mm3 at study entry

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the (preliminary) efficacy of IFN-? as adjunctive treatment in combination with standard therapy for the treatment of patients presenting with septic shock, by assessment of a series of surogate immunological parameters. ;Secondary Objective: A secondary aim will be to evaluate markers (including mHLA-DR expression) that are currently used to identify patients with immunoparalysis who will benefit from immunotherapy, and to monitor the patient’s immunological response to IFN-?.;Primary end point(s): The primary endpoint is the TNF-a secretion by ex vivo LPS-stimulated leukocytes as a marker of immunosuficiency/antimicrobial response. ;Timepoint(s) of evaluation of this end point: at admission and at days 0, 2, 7, 14, and 28