Trial reportCritical care (London, England)2012
A placebo-controlled, double-blind, dose-escalation study to assess the safety, tolerability and pharmacokinetics/pharmacodynamics of single and multiple intravenous infusions of AZD9773 in patients with severe sepsis and septic shock.
Trial report in Critical care (London, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 28 citations in OpenAlex.
- Assessing Monoclonal and Polyclonal Antibodies in Sepsis and Septic Shock: A Systematic Review of Efficacy and Safety.International journal of molecular sciences · 2025Pooled it
- Antitumor necrosis factor therapy is associated with improved survival in clinical sepsis trials: a meta-analysis.Critical care medicine · 2013Pooled it
- Population pharmacokinetic/pharmacodynamic modelling of the anti-TNF-α polyclonal fragment antibody AZD9773 in patients with severe sepsis.Journal of pharmacokinetics and pharmacodynamics · 2012Trial
- Dichotomous Role of Tumor Necrosis Factor in Pulmonary Barrier Function and Alveolar Fluid Clearance.Frontiers in physiology · 2021Review
- Re-Evaluating Biologic Pharmacotherapies that Target the Host Response during Sepsis.International journal of molecular sciences · 2019Review
- Post-exposure treatment of non-human primates lethally infected with Ebola virus with EBOTAb, a purified ovine IgG product.Scientific reports · 2017Article
- Shedding of the tumor necrosis factor (TNF) receptor from the surface of hepatocytes during sepsis limits inflammation through cGMP signaling.Science signaling · 2015Article
- Management of sepsis in neutropenic patients: 2014 updated guidelines from the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO).Annals of hematology · 2014Review
- Inflammation, myocardial dysfunction, and mortality in children with septic shock: an observational study.Pediatric cardiology · 2014Observational
- Determination of the safety and efficacy of therapeutic neutralization of tumor necrosis factor-α (TNF-α) using AZD9773, an anti-TNF-α immune Fab, in murine CLP sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2014Article
- After Xigris, researchers look to new targets to combat sepsis.Nature medicine · 2012Article
- The effect of polyclonal and monoclonal based antibodies as promising potential therapy for treatment of sepsis: A systematic review.New microbes and new infectionsReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionTumor necrosis factor-alpha (TNF-α), an early mediator in the systemic inflammatory response to infection, is a potential therapeutic target in sepsis. The primary objective of this study was to determine the safety and tolerability of AZD9773, an ovine, polyclonal, anti-human TNF-α Fab preparation, in patients with severe sepsis. Secondary outcomes related to pharmacokinetic (PK) and pharmacodynamic (PD) parameters.
methodsIn this double-blind, placebo-controlled, multicenter Phase IIa study, patients were sequentially enrolled into five escalating-dose cohorts (single doses of 50 or 250 units/kg; multiple doses of 250 units/kg loading and 50 units/kg maintenance, 500 units/kg loading and 100 units/kg maintenance, or 750 units/kg loading and 250 units/kg maintenance). In each cohort, patients were randomized 2:1 to receive AZD9773 or placebo.
resultsSeventy patients received AZD9773 (n=47) or placebo (n=23). Baseline characteristics were similar across cohorts. Mean baseline APACHE score was 25.9. PK data demonstrated an approximately proportional increase in concentration with increasing dose and a terminal half-life of 20 hours. For the multiple-dose cohorts, serum TNF-α concentrations decreased to near-undetectable levels within two hours of commencing AZD9773 infusion. This suppression was maintained in most patients for the duration of treatment. AZD9773 was well tolerated. Most adverse events were of mild-to-moderate intensity and considered by the reporting investigator as unrelated to study treatment.
conclusionsThe safety, PK and PD data support the continued evaluation of AZD9773 in larger Phase IIb/III studies.
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Registered trials
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.