The Effects of Interferon-gamma on Sepsis-induced Immunoparalysis

NCT01649921 | Completed Phase 3 DMC

• 1 other identifier: IFN_sepsis
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sepsis; Septic Shock

Keywords

Sepsis; SIRS; Septic shock; Immunoparalysis; Interferon-gamma

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is the tumor necrosis factor (TNF)-α secretion by ex vivo lipopolysaccharide (LPS)-stimulated leukocytes as a marker of immunosufficiency/antimicrobial response.

  at admission and at days 0, 2, 7, 14 and 28

Secondary Outcomes (11)

• Outcome of bacterial infection (occurrence of secondary and/or opportunistic infections, duration of antibacterial treatment, microbiological evaluation)

  At days 0, 2, 7, 14 and 28

• Hemodynamic stability (noradrenalin infusion rate, amount of infused fluids per day, amount of urine produced per day, daily fluid balance)

  At days 0, 2, 7, 14 and 28

• Mortality (including time to death) at week 2 and week 6 after end of treatment (all causes)

  At days 14 and 28

• Length of stay at ICU and duration of hospitalization

  At days 28 and 56

• Organ function

  at days 0, 14, and 28

Study Arms (2)

Interferon-gamma

ACTIVE COMPARATOR

Drug: Interferon-gamma, Recombinant

Saline 0.9%

PLACEBO COMPARATOR

Other: Saline 0.9%

Interventions

Interferon-gamma, Recombinant DRUG

Interferon-gamma (Immukine, Boehringer-Ingelheim, Alkmaar, the Netherlands), 100mcg subcutaneously, on days 0-2-4-7-9-11. Interferon-gamma treatment will be initiated when the noradrenalin dose is reduced to 50% of maximum dose, ensuring that the sepsis-induced pro-inflammatory phase has passed

Interferon-gamma

Saline 0.9% OTHER

subcutaneous administration on days 0, 2, 4, 7, 9, and 11.

Saline 0.9%

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, Netherlands

Location

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Interferon-gamma; Sodium Chloride

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Macrophage-Activating Factors; Lymphokines; Proteins; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Peter Pickkers, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2012
• First Posted: July 25, 2012
• Study Start: November 1, 2012
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: September 29, 2017

Record last verified: 2014-04

Locations

NL (1)