NCT03332225: PROVIDE

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

Completed Phase 2 Last updated 29 July 2020

What this trial tests

Phase 2 trial testing Anakinra in Sepsis in 36 participants. Completed in 31 December 2019.

Timeline

15 December 2017

Primary endpoint
31 December 2019

31 December 2019

Quick facts

Lead sponsor	Hellenic Institute for the Study of Sepsis
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	36
Start date	15 December 2017
Primary completion	31 December 2019
Estimated completion	31 December 2019
Sites	13 locations across Greece

Drugs / interventions tested

• Anakinra (ANAKINRA) — full drug profile →
• Recombinant human interferon-gamma — full drug profile →
• Placebo

Conditions studied

• Sepsis — all drugs for Sepsis →
• Macrophage Activation Syndrome — all drugs for Macrophage Activation Syndrome →

Sponsor

Hellenic Institute for the Study of Sepsis

Who can join

18 and older, any sex, with Sepsis or Macrophage Activation Syndrome. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure.
   Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, et al · · 2020 · cited 1621× · PMID 32320677 · DOI 10.1016/j.chom.2020.04.009
2. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?
   Liu B, Li M, Zhou Z, Guan X, et al · · 2020 · cited 507× · PMID 32291137 · DOI 10.1016/j.jaut.2020.102452
3. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions.
   Jamilloux Y, Henry T, Belot A, Viel S, et al · · 2020 · cited 486× · PMID 32376392 · DOI 10.1016/j.autrev.2020.102567
4. Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options.
   Liu D, Huang SY, Sun JH, Zhang HC, et al · · 2022 · cited 407× · PMID 36209190 · DOI 10.1186/s40779-022-00422-y
5. Macrophage Activation-Like Syndrome: A Distinct Entity Leading to Early Death in Sepsis.
   Karakike E, Giamarellos-Bourboulis EJ. · · 2019 · cited 223× · PMID 30766533 · DOI 10.3389/fimmu.2019.00055
6. Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome.
   Mehta P, Cron RQ, Hartwell J, Manson JJ, et al · · 2020 · cited 207× · PMID 32373790 · DOI 10.1016/s2665-9913(20)30096-5
7. Favorable Anakinra Responses in Severe Covid-19 Patients with Secondary Hemophagocytic Lymphohistiocytosis.
   Dimopoulos G, de Mast Q, Markou N, Theodorakopoulou M, et al · · 2020 · cited 175× · PMID 32411313 · DOI 10.1016/j.chom.2020.05.007
8. Neutrophil pyroptosis: new perspectives on sepsis.
   Liu L, Sun B. · · 2019 · cited 160× · PMID 30877336 · DOI 10.1007/s00018-019-03060-1