Trial reportIntensive care medicine2016
Protein C zymogen in severe sepsis: a double-blinded, placebo-controlled, randomized study.
Trial report in Intensive care medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Efficacy and safety of anticoagulant therapy in sepsis: A systematic review and meta-analysis.The Journal of international medical research · 2026Pooled it
- Efficacy and safety of anticoagulant therapy in patients with sepsis: a meta-analysis of randomized controlled trials.Thrombosis journal · 2025Article
- Protein C in adult patients with sepsis: from pathophysiology to monitoring and supplementation.Journal of anesthesia, analgesia and critical care · 2025Review
- The transition of the criteria for disseminated intravascular coagulation and the targeted patients in randomized controlled trials over the decades: a scoping review.Thrombosis journal · 2024Article
- Endothelial dysfunction and immunothrombosis in sepsis.Frontiers in immunology · 2023Review
- A Pathophysiological Perspective on the SARS-CoV-2 Coagulopathy.HemaSphere · 2020Review
- ICM focus on thrombosis and bleeding.Intensive care medicine · 2017Article
- Is protein C zymogen really ineffective for ALL cases of sepsis including septic DIC?Intensive care medicine · 2017Article
- Estimation bias resulting from sparse data: response to comments by Zhang and Ren.Intensive care medicine · 2016Article
- Estimation bias resulting from sparse data.Intensive care medicine · 2016Article
Corrections and comments
- Commented on by
Authors and funding
9 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo determine whether protein C zymogen (protein C concentrates or human protein C) improves clinically relevant outcomes in adult patients with severe sepsis and septic shock.
methodsThis is a randomized, double-blind, placebo-controlled, parallel-group trial that from September 2012 to June 2014 enrolled adult patients with severe sepsis or septic shock and high risk of death and of bleeding (e.g., APACHE II greater than 25, extracorporeal membrane oxygenation or disseminated intravascular coagulopathy). All patients completed their follow-up 90 days after randomization and data were analyzed according to the intention-to-treat principle. Follow-up was performed at 30 and 90 days after randomization. The primary endpoint was a composite outcome of prolonged intensive care unit (ICU) stay and/or 30-day mortality. Secondary endpoints included mortality.
resultsThe study was stopped early in a situation of futility for the composite outcome of prolonged ICU stay and/or 30-day mortality that was 79 % (15 patients) in the protein C zymogen group and 67 % (12 patients) in the placebo group (p = 0.40) and for a concomitant safety issue: ICU mortality was 79 % (15 patients) in the protein C zymogen group vs 39 % (7 patients) in the placebo group (p = 0.020), and 30-day mortality was 68 vs 39 % (p = 0.072).
conclusionProtein C zymogen did not improve clinically relevant outcomes in severe sepsis and septic shock adult patients. Given its high cost and the potential increase in mortality, the use of this drug in adult patients should be discouraged.
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.