The aim of ImmunoSep is to study if personalized immunotherapy targeting either fulminant hyper-inflammation or immunoparalysis is able to improve sepsis outcomes.
ID
Source
Brief title
Condition
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The difference in the mean total SOFA (Sequential Organ Failure Assessment)
score until day 9 after randomization.
Secondary outcome
- 28-day mortality
- 90-day mortality
- The change of mean total SOFA score on day 15 of the end of treatment
- The impact of personalized immunotherapy on the reversal of
hyper-inflammation or immunoparalysis.
- The impact of personalized immunotherapy on the resolution of infection
leading to study enrolment.
- The development of genomic, epigenomic, proteomic, metabolomic and
microbiomic surrogate biomarkers for the primary and secondary endpoints.
Background summary
Sepsis is a life-threatening organ dysfunction that results from the
dysregulated host response to an infection. Accumulating knowledge suggests
that there is a spectrum of dysregulation in this response. On the one end of
this spectrum there are patients whose immune response is characterized by
fulminant hyper-inflammation. On the other end of this spectrum there are
patients whose immune response is characterized by immunoparalysis. Ferritin
and HLA-DR expression on monocytes are diagnostic biomarkers for
hyper-inflammation and immunoparalysis, respectively. Personalized
immunotherapy with anakinra for hyper-inflammation and recombinant human
interferon gamma for immunoparalysis could be able to improve sepsis outcomes.
Study objective
The aim of ImmunoSep is to study if personalized immunotherapy targeting either
fulminant hyper-inflammation or immunoparalysis is able to improve sepsis
outcomes.
Study design
Prospective, multicentered, interventional, randomized, double-blind,
double-dummy, placebo-controlled clinical trial
Intervention
Immunotherapy with iv anakinra 200 mg three times daily (every eight hours) or
sc recombinant human interferon gamma-1b 100 µg once every other day for 15
days.
Study burden and risks
Anakinra and interferon-gamma are both licensed agents for other diseases.
Therefore, the safety profile of these treatments are well-known. A similar
safety profile has been reported for treatment of severely ill patients and
patients with sepsis. To this end, no potential harmful risks are expected in
this cohort. Potential side effect are expected to be mild and patients will
recover from an occurring side effect without any expected complications.
Additional burden of blood collections and swabs are minimal and the blood
collections for this study will be combined with clinically initiated blood
collections where possible.
Michalakopoulou str 88
Athene 11528
GR
Michalakopoulou str 88
Athene 11528
GR
Listed location countries
Age
Inclusion criteria
- Age equal to or above 18 years.
- Both genders.
- In case of women, unwillingness to become 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 (CAP) or hospital-acquired pneumonia (HAP) or
ventilator-associated pneumonia (VAP) or primary bacteremia (BSI).
- Sepsis defined by the Sepsis-3 definitions. More precisely, sepsis is defined
as the presence of total SOFA (sequential organ failure assessment score) equal
to 2 or more for patients who are admitted with infection at the emergency
department OR as any increase of admission SOFA by 2 or more points for
patients already hospitalized.
- Patients with signs of fulminant hyper-inflammation or sepsis-associated
immunoparalysis. Since the state of hyper-inflammation is considered more
life-threatening than the state of immunoparalysis, patients with lab findings
of both immune states are allocated to treatment targeting hyper-inflammation.
It is explicitly stated that patients diagnosed with COVID-19 infection may
participate only in the fulminant hyper-inflammation arm
- Time from classification into sepsis by the Sepsis-3 definitions and start of
blind intervention less than 72 hours.
Exclusion criteria
- Age below 18 years.
- Denial for written informed consent.
- Acute pyelonephritis or intraabdominal infection, meningitis or skin
infection.
- Any stage IV malignancy.
- Neutropenia defined as an absolute neutrophil count lower than 1,500/mm3.
- Any *do not resuscitate* decision in the hospital.
- 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 intravenous intake of corticosteroids at a daily dose equal or
greater than 0.4 mg/kg 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-005768-74-NL |
| CCMO | NL76706.091.21 |