Trial reportIntensive care medicine2021
Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial.
Trial report in Intensive care medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 3 syntheses or guidelines pooled it, 86 citations in OpenAlex.
- Targeting capillary leak in experimental sepsis and endotoxemia: a systematic review of therapeutic agents, methods and models in animal studies.Critical care (London, England) · 2026Pooled it
- Predictive enrichment using biomarkers in studies of critically-ill patients with sepsis: a systematic review.Critical care (London, England) · 2025Pooled it
- Assessing Monoclonal and Polyclonal Antibodies in Sepsis and Septic Shock: A Systematic Review of Efficacy and Safety.International journal of molecular sciences · 2025Pooled it
- Trial
- The ADESTE trial: A phase 2 study of enibarcimab, a monoclonal antibody targeting adrenomedullin, in acute heart failure.ESC heart failure · 2025Trial
- Influence of adrenomedullin on the enzymatic activity of dipeptidyl peptidase 3Journal of enzyme inhibition and medicinal chemistry · 2026Article
- [Pharmacological immunomodulation in sepsis].Medizinische Klinik, Intensivmedizin und Notfallmedizin · 2026Review
- Association of perioperative bioactive adrenomedullin with early postoperative organ dysfunction after major hepatic resection: An exploratory observational study.Langenbeck's archives of surgery · 2026Observational
- Update on sepsis treatment.Journal of intensive care · 2026Review
- Host-directed immune therapies: a second front in the battle against sepsis.The Journal of clinical investigation · 2026Review
- Measuring and managing pulmonary edema in ARDS: a narrative review.Critical care (London, England) · 2026Review
- Challenges in early detection and prognostication of sepsis: new approaches from the emergency department and intensive care unit.EClinicalMedicine · 2026Review
- Modulating Vimentin: A Systems-Level Therapeutic Strategy for Sepsis and Complex Diseases.Life (Basel, Switzerland) · 2026Article
- The "cytokine storm" in infection and sepsis: win the battle but lose the war.Military Medical Research · 2026Review
- Endothelial barrier and sepsis: mechanisms and potential therapeutic strategies.Military Medical Research · 2026Review
- Septic shock in the era of precision medicine: rethinking fluids, vasopressors, and immunomodulation.Frontiers in medicine · 2026Review
- Beyond antimicrobials: a host-directed precision pharmacotherapy framework for septic shock.Frontiers in medicine · 2026Article
- Decoding lung-kidney interactions in sepsis: an integrated view of molecular mechanisms, pathophysiology, and therapeutic interventions.Frontiers in immunology · 2026Review
- GC-MS metabolomics reveals potential biomarkers for infection-specific subtypes in sepsis.Open medicine (Warsaw, Poland) · 2026Article
- Adrenomedullin as an Immunomodulator of CD14Journal of clinical and translational hepatology · 2025Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 18 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeInvestigate safety and tolerability of adrecizumab, a humanized monoclonal adrenomedullin antibody, in septic shock patients with high adrenomedullin.
methodsPhase-2a, double-blind, randomized, placebo-controlled biomarker-guided trial with a single infusion of adrecizumab (2 or 4 mg/kg b.w.) compared to placebo. Patients with adrenomedullin above 70 pg/mL, < 12 h of vasopressor start for septic shock were eligible. Randomization was 1:1:2. Primary safety (90-day mortality, treatment emergent adverse events (TEAE)) and tolerability (drug interruption, hemodynamics) endpoints were recorded. Efficacy endpoints included the Sepsis Support Index (SSI, reflecting ventilator- and shock-free days alive), change in Sequential-related Organ Failure Assessment (SOFA) and 28-day mortality.
results301 patients were enrolled (median time of 8.5 h after vasopressor start). Adrecizumab was well tolerated (one interruption, no hemodynamic alteration) with no differences in frequency and severity in TEAEs between treatment arms (TEAE of grade 3 or higher: 70.5% in the adrecizumab group and 71.1% in the placebo group) nor in 90-day mortality. Difference in change in SSI between adrecizumab and placebo was 0.72 (CI -1.93-0.49, p = 0.24). Among various secondary endpoints, delta SOFA score (defined as maximum versus minimum SOFA) was more pronounced in the adrecizumab combined group compared to placebo [difference at 0.76 (95% CI 0.18-1.35); p = 0.007]. 28-day mortality in the adrecizumab group was 23.9% and 27.7% in placebo with a hazard ratio of 0.84 (95% confidence interval 0.53-1.31, log-rank p = 0.44).
conclusionsOverall, we successfully completed a randomized trial evaluating selecting patients for enrolment who had a disease-related biomarker. There were no overt signals of harm with using two doses of the adrenomedullin antibody adrecizumab; however, further randomized controlled trials are required to confirm efficacy and safety of this agent in septic shock patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.