A Phase 2 interventional study of Anakinra and Recombinant human interferon-gamma in Sepsis and Macrophage Activation Syndrome, sponsored by Hellenic Institute for the Study of Sepsis. Completed at 13 sites in Greece. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-07-29.
Sponsored by Hellenic Institute for the Study of Sepsis · Phase 2, Interventional, and Treatment
Help build ClinicalTrials.gg — short surveys, remote interviews or testing, in your language. Take part →
Among 16 studies in Sepsis by Hellenic Institute for the Study of Sepsis — 4 open to participants now, 6 under way, 4 of them phase 3. Sepsis · Hellenic Institute for the Study of Sepsis.
Among the 16 studies in Sepsis by Hellenic Institute for the Study of Sepsis, this one is the 13th largest by enrollment of the 13 interventional ones that give a count, is one of 4 that started in 2017, is one of 4 in phase 2, and was the 3rd registered.
2,417 studies on the registry are indexed under Sepsis; 542 are open to participants now.
Browse Sepsis studies →4 of the 16 studies in Sepsis by Hellenic Institute for the Study of Sepsis are open now, in 1 country. Recruiting first, the newest first:
Hellenic Institute for the Study of Sepsis · Sites in Greece
Ages 18+
Hellenic Institute for the Study of Sepsis · Sites in Greece
Ages 18+
Hellenic Institute for the Study of Sepsis · Sites in Greece
Ages 18+
Hellenic Institute for the Study of Sepsis · Sites in Greece
Ages 18+
By country, each count listing its studies:
Of the 318 Sepsis studies recruiting now, 213 (67%) set no upper age limit and 53 (17%) stop at 75 or younger; 68 take children under 18; 42 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
16 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 2 5 · Phase 3 7
First in 2017; this study’s year is marked. 4 started in 2017.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 36 is below the median of 102 across 1,166 interventional studies indexed under Sepsis.
Median enrollment 252 across the 13 interventional studies, 200 across the 3 observational. Of the 9 that completed or were terminated, 0 (0%) have results posted.
This tab as a report to print or save as PDF → With an account.
Hellenic Institute for the Study of Sepsis is the lead sponsor of 32 studies on the registry; 7 are open to participants now.
2 of the studies in Sepsis by Hellenic Institute for the Study of Sepsis that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT06694701Hellenic Institute for the Study of SepsisEmapalumab Treatment For Anticipated Clinical Benefit In Sepsis Driven By The Interferon-Gamma Endotype (The EMBRACE Trial) | 2026-11 |
| NCT07927621Hellenic Institute for the Study of SepsisViscoelastic Coagulation Monitoring for Early Identification of Sepsis: The VISION II Study | 2027-05 |
Add all 2 to your calendar (.ics) → With an account.
Among the 16 studies in Sepsis by Hellenic Institute for the Study of Sepsis, from their registry updates:
This tab as a report to print or save as PDF → With an account.
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.
Sepsis is a life-threatening organ dysfunction that results from the dysregulated host response to an infection. Accumulating knowledge suggests that this dysregulated host response has a broad spectrum where some patients lie to the two extremes of this spectrum whereas the majority of patients lie in between. The first extreme encompasses patients who are dominated from a hyper-inflammatory response to an infectious insult. On the other extreme lie patients who do not have any hyper-inflammatory response; instead these patients are dominated by an exhausted immune response to an infectious stimulus. The remaining patients have features of both hyper- and hypo-inflammatory responses.
Randomized clinical trials (RCTs) that have investigated the effects of immunotherapy in sepsis have all failed to establish beneficial effects for the patients. The reasons for that are multiple but one of the most important is the current notion that sepsis is a complex disorder with heterogeneity regarding patient characteristics. Thus, it is necessary to try and find ways to personalise the immunomodulatory treatment of sepsis. In the clinical trial proposed here, two personalised approaches will be investigated.
Some 25 years ago, there were high expectations of the blockade of interleukin (IL)-1 in sepsis using the human recombinant IL-1 receptor antagonist, anakinra. The expectations were based on animal experiments as well as positive results in a single-centre clinical trial. However, in a large international trial, anakinra did not show benefit over placebo. Still, it became clear from this study, enrolling 906 patients that intravenous anakinra was a very safe drug: there was neither excess mortality in these critically ill patients, nor increased susceptibility to secondary infections. In a post-hoc analysis of this trial published in 2016, it was demonstrated that a subgroup of 34 patients showed a clinical picture compatible with macrophage activation syndrome. Since bone marrow was not performed in these patients, the investigators prefer to call this macrophage activation like syndrome (MALS). MALS is a dreaded complication with a mortality rate in the order of 70%. The post-hoc analysis showed that patients receiving anakinra had 30% significant survival benefit compared to those receiving placebo. From these data it can be concluded that it is important to recognize patients with this complication of sepsis and that anakinra might be a beneficial drug.
A survey of the database of sepsis patients in the Hellenic Sepsis Study Group revealed that 5% of the patients with septic shock suffered from MALS. It was found in this study that MAS can be easily and reliably diagnosed by measuring ferritin in the blood. A cut off of 4.420ng/ml had specificity more than 97%.
Another important clinical phenomenon in sepsis is that patients may run into a phase of immunoparalysis. In this situation, the immune cells do not produce any more proinflammatory cytokines and switch to production of anti-inflammatory cytokines such as IL-10; they also loose important functional markers such HLA-DR. Patients with immunoparalysis have a 50% risk of dying in the subsequent 28 days. There is evidence from preclinical studies and from the endotoxin challenge model in human volunteers that immunoparalysis is reversible at least to some extent. The best candidate drug for this would be interferon gamma (IFNγ). Immunosuppression established in healthy volunteers after experimental endotoxemia was reversed after administration of recombinant human interferon-gamma (rhIFNγ). rhIFNγ was also investigated for this purpose in nine patients at septic shock in a small open-label and non-randomized clinical trial; reversal of immunoparalysis was achieved. The extensive experience with IFNγ teaches that it is a safe drug, the main side effect being fever and flu-like syndrome, which can be mitigated by premedication with a prostaglandin inhibitor like paracetamol. In patients with autoimmune diseases like systemic lupus erythematosus (SLE) and multiple sclerosis flares of the disease induced by IFNγ have been described. So these diseases are contraindications for the drug.
The purpose of this study is to investigate in a randomised placebo-controlled clinical trial with a double-dummy design in patients with septic shock, whether personalised immunotherapy directed against either MALS or immunoparalysis is able to change the perspective for these critically ill patients.
MALS is considered as a more direct life-threatening manifestation of sepsis than immunoparalysis. For that reason all patients will be randomised with evidence of MALS for anakinra or placebo, irrespective the state of immunity as measured by HLA-DR positivity.
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 allocated to placebo or immunotherapy treatment according to their needs.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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 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 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 anakinra
Also known as: Kineret
Treatment with recombinant human interferon-gamma
Also known as: Imukin
Treatment with Placebo
Also known as: Saline Solution
Mortality
Mortality will be compared between the groups of treatment
Time frame: 28 days
Mortality
Mortality will be compared between the groups of treatment
Time frame: 90 days
Time to decrease of SOFA score by more than 50%
The time to decrease of SOFA score by more than 50% will be compared between the groups of treatment
Time frame: 28 days
Time to infection resolution
The time to infection resolution will be compared between the groups of treatment
Time frame: 28 days
Duration of hospitalisation
The duration of hospitalisation will be compared between the groups of treatment
Time frame: 28 days
Number of secondary infections
The number of secondary infections will be compared between the groups of treatment
Time frame: 28 days
Cytokine stimulation
Cytokine stimulation from peripheral blood mononuclear cells will be compared between the groups of treatment
Time frame: 4 days
Cytokine stimulation
Cytokine stimulation from peripheral blood mononuclear cells will be compared between the groups of treatment
Time frame: 7 days
Gene expression
Gene expression of peripheral blood mononuclear cells will be compared between the groups of treatment
Time frame: 7 days
Gut microbiome changes
Gut microbiome changes will be compared between the groups of treatment
Time frame: 7 days
Epigenetic changes
Epigenetic changes of circulating monocytes will be compared between the groups of treatment
Time frame: 7 days
Classification of the immune function
Classification of the immune function of screened patients not characterized with MALS neither with hypo-inflammation
Time frame: 28 days
Plan to share: No
Ran from Dec 2017 to primary completion in Dec 2019, 24 months.
Of 43 non-industry phase 2 interventional studies under Sepsis, half reached primary completion within 30 months of starting (the median), counting those still running; a quarter within 16 and three quarters within 35. This study's 24 months is below that.
Counting every sponsor, half of 60 studies reached it within 29 months; a quarter within 17 and three quarters within 37.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jul 2020. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Interleukin 1 Receptor Antagonist Protein
Hellenic Institute for the Study of Sepsis