Sepsis-Associated Purpura Fulminans International Registry - Europe

Completed

• Conditions: Sepsis

• Registration Number: NCT02238795
• Lead Sponsor: Jena University Hospital

Brief Summary

Sepsis-associated Purpura fulminans (SAPF) is a rare life-threatening condition. It is characterized by multiple skin lesions which rapidly progress to necrosis and gangrene. SAPF is a manifestation of widespread clot formation in small blood vessels which emerges secondarily to severe bacterial and viral infections. The clinical presentation of SAPF is dominated by symptoms of severe sepsis and multiple organ failure which are further aggravated by the massive skin lesions.

At present, there are no evidence-based guidelines for the medical management of SAPF. With numerous therapeutic approaches in use, there are no consistent comparisons of their efficacy. Altered role of causal pathogens following the introduction of meningococcal and pneumococcal prophylactic vaccines also remains to be investigated.

The goal of the registry is comprehensive collection and evaluation of information concerning the epidemiology, morbidity, therapy and outcome of SAPF.

Detailed Description

Purpura fulminans is the clinical manifestation of disseminated thrombosis in dermal and systemic microcirculation. This rare disease is frequently associated with multiple organ failure and represents a life-threatening condition with mortality exceeding 50 %. In the vast proportion of cases, the condition has been shown to emerge secondary to acquired Protein C deficiency associated with severe sepsis, mostly of meningococcal or pneumococcal origin.

A consistent therapeutic approach to sepsis-associated Purpura fulminans (SAPF) has not been established yet. With exaggerated pro-coagulant activity being confirmed as the key pathogenic aspect, several treatment modalities aiming at the balance restoration in the coagulation cascade have been considered.

SAPF causality might have been substantially altered in the wake of widespread meningococcal and pneumococcal vaccination. There are neither evidence-based treatment guidelines nor comparative evaluation of the efficacy of different therapeutic approaches.

The present registry aims at a) large-scale data accumulation and comprehensive evaluation of the incidence, causality and current treatment strategies of SAPF, b) comparative assessment of treatment strategies including or not including protein C supplementation c) identification of patient subgroups of particular eligibility for Protein C treatment, as judged by established criteria of disease severity assessment, d) feedback of aggregated data to registry contributors, thus permitting quality management and standard updates, e) dissemination of data evaluation summaries and recommendations for the use of Protein C formulations in clinical routine, f) elaboration of a framework for SAPF treatment recommendations and guidelines.

The registry comprises prospective, multicentric open-label data collection on the current state of incidence and management of SAPF, regardless of the etiopathogenic background. It will include comprehensive records on diagnosis, morbidity and management of SAPF, supplied in the form of electronic case report forms (eCRFs) by the participating centers over a period of three years.

Study Timeline

• Study First Submitted: 2014-09-10
• Study First Submitted QC: 2014-09-10
• Study First Posted: 2014-09-12
• Study Start: 2016-04
• Primary Completion: 2020-09-30
• Study Completion: 2020-09-30
• Results First Submitted: 2021-10-08
• Status Verified: 2025-03
• Results First Submitted QC: 2025-05-19
• Last Update Submitted: 2025-05-19
• Results First Posted: 2025-05-21
• Last Update Posted: 2025-05-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

• Diagnosis of sepsis and Purpura fulminans
• Signed informed consent

Exclusion Criteria

• Premature neonates (below gestational age of 36 weeks)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Mortality	during hospital stay (estimated up to 3 months)	All-cause in-hospital mortality

Secondary Outcome Measures

Name	Time	Method
Hospital Stay	duration of hospital stay, up to 3 months	Hospital stay (in days), patients were observed through hospital stay as long as it took
Protein C	until day 7	Administration of Protein C
Extent and Severity of Purpura Fulminans Lesions	7 days	Extent and severity of Purpura fulminans lesions: Number of lesions with purpura fulminans
Duration of ICU Stay	during ICU stay (estimated up to 3 months)	Duration of hospitalization in an ICU
Mean Total Sepsis-related Organ Failure Assessment (SOFA) Score	day 7	Mean total Sepsis-related organ failure assessment (SOFA) score at day 7, range 0-24 points, higher scores are worse.; The total SOFA score is the sum of the subscores of central nervous system, cardiovascular system, respiratory system, coagulation, liver and renal function. The range of all subscores is from 0 to 4, with 4 points indicating the worst outcome.
Adverse Drug Reaction: Bleeding	during ICU stay	Occurence of Bleeding (Adverse drug reaction)
Adverse Drug Reaction: Thrombotic Events	during ICU stay	Occurence of thrombotic events (Adverse Drug Reaction)
Adverse Drug Reactions: Visual Nerve Damage	during hospital stay (estimated up to 3 months)	Adverse Drug Reaction related to specific PF treatment: Visual nerve damage
Amputation	during ICU stay	Need for amputation

Trial Locations

Locations (3)

University Hospital Jena, Klinik für Anästhesiologie und Intensivmedizin; 🇩🇪 Jena, Germany

University Hospital Jena, Klinik für Kinder- und Jugendmedizin; 🇩🇪 Jena, Germany

Klinikum der Universität München; 🇩🇪 Munich, Germany