Table 1 Characteristics of the main circulatory shock studies with predictive enrichment
From: Distinct host-response signatures in circulatory shock: a narrative review
Study (year) | Design | Study population | Population size | Predictive enrichment strategy | Variables used for enrichment | Intervention | Main results |
|---|---|---|---|---|---|---|---|
Klein et al. (2018) [40] | Post hoc analysis of the EUPHRATES trial | Septic shock patients with MODS | N = 194 (original study N = 450) | Biomarker-guided therapy | Endotoxin activity level between 0.6 and 0.89 | Polymyxin B hemoperfusion to remove bacterial endotoxin | Associated with an absolute mortality reduction at 28 days Secondary outcomes: benefit change in MAP from baseline to day 3 and days alive and free of mechanical ventilation |
Levi et al. (2020) [41] | Post hoc analysis of the SCARLET trial | Septic shock associated coagulopathy | N = 800 | Biomarker-guided therapy | Elevated coagulation markers (prothrombin fragment 1.2, thrombin–antithrombin complex, d-dimer) | Recombinant human soluble thrombomodulin | Associated with all-cause mortality reduction at 28 days |
Shakoory et al. (2016) [42] | Post hoc analysis of the phase III randomized interleukin-1 receptor antagonist trial | Sepsis patients with MODS and/or shock | N = 43 (original study N = 763) | Biomarker-guided therapy | Hepatobiliary dysfunction and disseminated intravascular coagulation as features of macrophage activation syndrome | Anakinra (recombinant interleukin-1 receptor antagonist) | Significant improvement in survival at 28 days |
Bellomo et al. (2020) [45] | Post hoc analysis of the ATHOS-3 trial | catecholamine-resistant vasodilatory shock patients (sepsis, pancreatitis, post operative vasoplegia) | N = 321 | Biomarker-guided therapy | Serum renin concentrations | Angiotensin II | In patients with renin concentrations above the study population median, angiotensin II significantly reduced 28-day mortality |
Laterre et al. (2020) [47] | The AdrenOSS-2 phase 2a biomarker-guided trial | Septic shock with high Bio-ADM patients | N = 301 | Biomarker-guided therapy | Circulating Bio-ADM (> 70 pg/mL) | Adrecizumab (a humanized monoclonal adrenomedullin antibody) | Primary endpoint: good tolerance of adrecizumab Secondary endpoint: the reduction in SOFA score was significantly higher in the treatment group vs placebo |
Van Lier et al. (2022) [49] | Post hoc analysis of the AdrenOSS-2 trial | Septic shock with high Bio-ADM patients | N = 249 | Biomarker-guided therapy | Post hoc enrichment strategy based on low cDPP3 (< 50 ng/mL) | Adrecizumab (a humanized monoclonal adrenomedullin antibody) | In patients with low cDPP3 levels, Adrecizumab significantly reduced 28-day mortality |
Karakas et al. (2022) [50] | The ACCOST-HH biomarker-guided trial | Cardiogenic shock with high Bio-ADM patients | N = 150 | Biomarker-guided therapy | Circulating Bio-ADM (> 70 pg/mL) | Adrecizumab (a humanized monoclonal adrenomedullin antibody) | Adrecizumab was well tolerated but did not decrease the need for cardiovascular organ support (primary endpoint) or improve survival at days 30 and 90 |
Seymour et al. (2019) [15] | Post hoc analysis of observational studies and clinical trials | Sepsis and septic shock patients | N = 20 189 (the SENECA derivation cohort) | Phenotyping (latent class analysis, consensus K-means clustering) | 29 readily available clinical and biological variables on admission | Early goal-directed therapy in septic shock patients (ProCESS trial) | The estimated treatment effects were variable across the different identified four phenotypes (α, β, γ, and δ) with a significant interaction between early goal-directed therapy and phenotypes in the ProCESS trial |
Antcliffe et al. (2019) [53] | Post hoc analysis of the VANISH trial | Septic shock patients | N = 176 | Phenotyping (hierarchical clustering) | Genome-wide gene expression profiling (transcriptomic data) | Hydrocortisone | Two endotypes were identified: SRS1 (immunosuppressed) and SRS2 (immunocompetent). Hydrocortisone use was associated with increased mortality in septic shock patients assigned in the SRS2 endotype |
Thau et al. (2022) [54] | Post hoc analysis of the PROPPR trial | Severe trauma patients with hemorrhagic shock | N = 478 | Phenotyping (latent class analysis) | 36 plasma biomarkers of inflammation, endothelial dysfunction, and coagulation | Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 Ratio | Two trauma subphenotypes (TS-1 and TS-2) were identified. In patients assigned to TS-2 (lower plasma concentrations of IL-8 and TNF-α), a 1:1:1 transfusion ratio was associated with significantly reduced risk for 30-day mortality |