ReviewCritical care (London, England)2012
Drotrecogin alfa (activated)...a sad final fizzle to a roller-coaster party.
Review 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 19 papers, 1 of them a synthesis 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
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Nebulized anticoagulants for acute lung injury - a systematic review of preclinical and clinical investigations.Critical care (London, England) · 2012Pooled it
- Can Neurocritical Care Guidelines Developed in High-Income Countries be Relevant to Low- and Middle-Income Countries?Neurocritical care · 2025Article
- Comprehensive literature review of protein C concentrate use in patients with severe congenital protein C deficiency.Research and practice in thrombosis and haemostasis · 2024Review
- Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.Journal of personalized medicine · 2024Review
- In-silico identification and prioritization of therapeutic targets of asthma.Scientific reports · 2023Article
- Therapeutic Potential of Annexins in Sepsis and COVID-19.Frontiers in pharmacology · 2021Review
- Antibacterial Fusion Protein BPI21/LL-37 Modification Enhances the Therapeutic Efficacy of hUC-MSCs in Sepsis.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury.Thrombosis and haemostasis · 2017Article
- Potential Immunotherapeutics for Immunosuppression in Sepsis.Biomolecules & therapeutics · 2017Review
- Targeting thrombomodulin to circulating red blood cells augments its protective effects in models of endotoxemia and ischemia-reperfusion injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Activation of Coagulation and Fibrinolysis in Acute Respiratory Distress Syndrome: A Prospective Pilot Study.Frontiers in medicine · 2016Article
- An extracorporeal blood-cleansing device for sepsis therapy.Nature medicine · 2014Article
- Review
- Clinical meaning of the GRADE rules.Intensive care medicine · 2014Article
- Recombinant human soluble thrombomodulin in sepsis-induced disseminated intravascular coagulation: a multicenter propensity score analysis.Intensive care medicine · 2013Article
- Antiplatelet therapy is associated with decreased transfusion-associated risk of lung dysfunction, multiple organ failure, and mortality in trauma patients.Critical care medicine · 2013Article
- New approaches to sepsis: molecular diagnostics and biomarkers.Clinical microbiology reviews · 2012Article
- Epidemiology and outcome of severe pneumococcal pneumonia admitted to intensive care unit: a multicenter study.Critical care (London, England) · 2012Observational
- A historical perspective on sepsis.The American journal of pathology · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Following the failure of PROWESS-SHOCK to demonstrate efficacy, Eli Lilly and Company withdrew drotrecogin alfa (activated) from the worldwide market. Drotrecogin was initially approved after the original trial, PROWESS, was stopped early for overwhelming efficacy. These events prompt consideration of both the initial approval decision and the later decision to withdraw. It is regrettable that the initial decision was made largely on a single trial that was stopped early. However, the decision to approve was within the bounds of normal regulatory practice and was made by many approval bodies around the world. Furthermore, the overall withdrawal rate of approved drugs remains very low. The decision to withdraw was a voluntary decision by Eli Lilly and Company and likely reflected key business considerations. Drotrecogin does have important biologic effects, and it is probable that we do not know how best to select patients who would benefit. Overall, there may still be a small advantage to drotrecogin alfa, even used non-selectively, but the costs of determining such an effect with adequate certainty are likely prohibitive, and the point is now moot. In the future, we should consider ways to make clinical trials easier and quicker so that more information can be available in a timely manner when considering regulatory approval. At the same time, more sophisticated selection of patients seems key if we are to most wisely test agents designed to manipulate the septic host response.
Indexed as
Identifiers
What OpenQuestion holds
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.