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A Trial of Validation and Restoration of Immune Dysfunction in Severe Infections and Sepsis (PROVIDE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03332225
Recruitment Status : Completed
First Posted : November 6, 2017
Last Update Posted : July 29, 2020
Sponsor:
Information provided by (Responsible Party):
Hellenic Institute for the Study of Sepsis

Brief Summary:
The aim of the study is to conduct one RCT of personalized immunotherapy in sepsis targeting patients who lie either on the predominantly hyper-inflammatory arm or on the predominantly hypo-inflammatory arm of the spectrum of the host response. These patients will be selected by the use of a panel of biomarkers and laboratory findings and they will be randomly allocated to placebo or immunotherapy treatment according to their needs.

Condition or disease Intervention/treatment Phase
Sepsis Macrophage Activation Syndrome Drug: Anakinra Drug: Recombinant human interferon-gamma Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Treatment with recombinant human interferon-gamma or anakinra
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Personalized Randomized Trial of Validation and Restoration of Immune Dysfunction in Severe Infections and Sepsis
Actual Study Start Date : December 15, 2017
Actual Primary Completion Date : December 31, 2019
Actual Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis

Arm Intervention/treatment
Experimental: Anakinra
Treatment with iv anakinra 200 mg three times daily (every eight hours) for seven days and sc 1ml N/S 0.9% every other day for 15 days
Drug: Anakinra
Treatment with anakinra
Other Name: Kineret

Placebo Comparator: IV Placebo
Treatment with iv 1ml N/S 0.9% three times daily (every eight hours) for seven days and sc 1ml N/S 0.9% every other day for 15 days
Drug: Placebo
Treatment with Placebo
Other Name: Saline Solution

Experimental: Recombinant human interferon-gamma
Treatment with sc recombinant human interferon-gamma every other day for a total of 15 days and with iv 1ml N/S 0.9% three times daily (every eight hours) for seven days
Drug: Recombinant human interferon-gamma
Treatment with recombinant human interferon-gamma
Other Name: Imukin




Primary Outcome Measures :
  1. Mortality [ Time Frame: 28 days ]
    Mortality will be compared between the groups of treatment


Secondary Outcome Measures :
  1. Mortality [ Time Frame: 90 days ]
    Mortality will be compared between the groups of treatment

  2. Time to decrease of SOFA score by more than 50% [ Time Frame: 28 days ]
    The time to decrease of SOFA score by more than 50% will be compared between the groups of treatment

  3. Time to infection resolution [ Time Frame: 28 days ]
    The time to infection resolution will be compared between the groups of treatment

  4. Duration of hospitalisation [ Time Frame: 28 days ]
    The duration of hospitalisation will be compared between the groups of treatment

  5. Number of secondary infections [ Time Frame: 28 days ]
    The number of secondary infections will be compared between the groups of treatment

  6. Cytokine stimulation [ Time Frame: 4 days ]
    Cytokine stimulation from peripheral blood mononuclear cells will be compared between the groups of treatment

  7. Cytokine stimulation [ Time Frame: 7 days ]
    Cytokine stimulation from peripheral blood mononuclear cells will be compared between the groups of treatment

  8. Gene expression [ Time Frame: 7 days ]
    Gene expression of peripheral blood mononuclear cells will be compared between the groups of treatment

  9. Gut microbiome changes [ Time Frame: 7 days ]
    Gut microbiome changes will be compared between the groups of treatment

  10. Epigenetic changes [ Time Frame: 7 days ]
    Epigenetic changes of circulating monocytes will be compared between the groups of treatment

  11. Classification of the immune function [ Time Frame: 28 days ]
    Classification of the immune function of screened patients not characterized with MALS neither with hypo-inflammation



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age equal to or above 18 years
  • Male or female gender
  • In case of women, unwillingness to remain pregnant during the study period
  • Written informed consent provided by the patient or by one first-degree relative/spouse in case of patients unable to consent
  • Community-acquired pneumonia or hospital-acquired pneumonia or ventilator-associated pneumonia or primary bacteremia or acute cholangitis
  • Sepsis defined by the Sepsis-3 definitions.
  • Patients with laboratory diagnosis of MALS or hypo-inflammation (immune-paralysis) based on two consecutive blood sampling with 24 hours apart. MALS is defined as the presence of ferritin >4,420 ng/ml and hypo-inflammation as HLA-DR expression on CD14-monocytes (co-expression) less than 30%

Exclusion Criteria:

  • Age below 18 years
  • Denial for written informed consent
  • Acute pyelonephritis or intraabdominal infection other than AC, meningitis or skin infection. It is explicitly stated that in the case of a patient with both AC and any other type of intraabdominal infection, the patient cannot be enrolled.
  • Any stage IV malignancy
  • Any do not resuscitate decision
  • In the case of BSI, patients with blood cultures growing coagulase-negative staphylococci or skin commensals or catheter-related infections cannot be enrolled.
  • Active tuberculosis (TB) as defined by the co-administration of drugs for the treatment of TB
  • Infection by the human immunodeficiency virus (HIV)
  • Any primary immunodeficiency
  • Oral or IV intake of corticosteroids at a daily dose equal or greater than 0.4 mg prednisone or greater the last 15 days
  • Any anti-cytokine biological treatment the last one month
  • Medical history of systemic lupus erythematosus
  • Medical history of multiple sclerosis or any other demyelinating disorder
  • Pregnancy or lactation. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03332225


Locations
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Greece
2nd Department of Critical Care Medicine
Athens, Haidari, Greece, 12462
4th Department of Internal Medicine
Athens, Haidari, Greece, 12462
Intensive Care Unit, Ioannina University Hospital
Ioánnina, Ioannina, Greece, 45500
Intensive Care Unit, Center for Accident Rehabilitation (KAT) of Athens
Athens, Kifissia, Greece, 14561
Department of Internal Medicine, Patras University Hospital
Patras, Rion, Greece, 26504
Intensive Care Unit, Alexandroupolis University Hospital
Alexandroupolis, Greece, 68100
1st Department of Pulmonary Medicine and Intensive Care Unit
Athens, Greece, 11527
Intensive Care Unit, "Latsio", Thriasio Elefsis General Hospital
Elefsína, Greece, 19600
Intensive Care Unit, "Koutlimbaneio & Triantafylleio" Larissa General Hospital
Larissa, Greece, 41221
Department of Internal Medicine, Larissa University Hospital
Larissa, Greece, 41334
Intensive Care Unit, "Tzanio" Piraeus General Hospital
Piraeus, Greece, 18536
Intensive Care Unit, "Aghios Dimitrios" Thessaloniki General Hospital
Salónica, Greece, 54634
Intensive Care Unit, "G.Gennimatas" Thessaloniki General Hospital
Salónica, Greece, 54635
Sponsors and Collaborators
Hellenic Institute for the Study of Sepsis
Investigators
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Principal Investigator: Antonios Papadopoulos, MD, PhD National Kapodistrian University of Athens, Medical School
Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hellenic Institute for the Study of Sepsis
ClinicalTrials.gov Identifier: NCT03332225    
Other Study ID Numbers: PROVIDE
2017-002171-26 ( EudraCT Number )
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: July 29, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hellenic Institute for the Study of Sepsis:
sepsis
macrophage activation syndrome
immunoparalysis
anakinra
recombinant human interferon-gamma
HLA-DR
Additional relevant MeSH terms:
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Sepsis
Toxemia
Immune System Diseases
Macrophage Activation Syndrome
Pathologic Processes
Infections
Systemic Inflammatory Response Syndrome
Inflammation
Lymphoproliferative Disorders
Immunoproliferative Disorders
Interferons
Interferon-gamma
Interleukin 1 Receptor Antagonist Protein
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Antirheumatic Agents