Sepsis-Associated Purpura Fulminans International Registry - Europe (SAPFIRE)

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.

Study Overview

• Status: Completed
• Conditions: Sepsis

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 Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• Germany
  • Jena, Germany
    • University Hospital Jena, Klinik für Anästhesiologie und Intensivmedizin
  • Jena, Germany
    • University Hospital Jena, Klinik für Kinder- und Jugendmedizin
  • Munich, Germany, 80337
    • Klinikum der Universität München

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with sepsis-associated Purpura fulminans

Description

Inclusion Criteria:

• Diagnosis of sepsis and Purpura fulminans
• Signed informed consent

Exclusion Criteria:

• Premature neonates (below gestational age of 36 weeks)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Purpura fulminans; Patients diagnosed with Purpura fulminans in association with sepsis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	All-cause in-hospital mortality	during hospital stay (estimated up to 3 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Stay	Hospital stay (in days), patients were observed through hospital stay as long as it took	duration of hospital stay, up to 3 months
Extent and Severity of Purpura Fulminans Lesions	Extent and severity of Purpura fulminans lesions: Number of lesions with purpura fulminans	7 days
Mean Total Sepsis-related Organ Failure Assessment (SOFA) Score	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.	day 7
Protein C	Administration of Protein C	until day 7
Duration of ICU Stay	Duration of hospitalization in an ICU	during ICU stay (estimated up to 3 months)
Adverse Drug Reactions: Visual Nerve Damage	Adverse Drug Reaction related to specific PF treatment: Visual nerve damage	during hospital stay (estimated up to 3 months)
Adverse Drug Reaction: Bleeding	Occurence of Bleeding (Adverse drug reaction)	during ICU stay
Adverse Drug Reaction: Thrombotic Events	Occurence of thrombotic events (Adverse Drug Reaction)	during ICU stay
Amputation	Need for amputation	during ICU stay

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vasopressor Days	Vasopressor-free days	during ICU stay (estimated up to 3 months)
Ventilator-free Days	Number of ventilator-free days	during ICU stay (estimated up to 3 months)
Renal Replacement Therapy	Duration (hours) of renal replacement therapy	during ICU stay (estimated up to 3 months)

Collaborators and Investigators

• Sponsor: Jena University Hospital
• Collaborators: Medical University of Vienna; Hannover Medical School; University Hospital, Essen; University Hospital, Basel, Switzerland; Ludwig-Maximilians - University of Munich; University Hospital Tuebingen; Universitätsklinikum Hamburg-Eppendorf; University Hospital of Cologne; Evangelisches Krankenhaus Bielefeld gGmbH; Insel Gruppe AG, University Hospital Bern
• Investigators: Study Chair: Frank M Brunkhorst, MD, Center for Clinical Studies, Jena University Hospital

Publications and helpful links

General Publications

• Brunkhorst FM, Patchev V. [Sepsis-associated Purpura Fulminans International Registry--Europe (SAPFIRE)]. Med Klin Intensivmed Notfmed. 2014 Nov;109(8):591-5. doi: 10.1007/s00063-014-0402-z. Epub 2014 Oct 29. German.

Helpful Links

• Registry website

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): September 30, 2020
• Study Completion (Actual): September 30, 2020

Study Registration Dates

• First Submitted: September 10, 2014
• First Submitted That Met QC Criteria: September 10, 2014
• First Posted (Estimated): September 12, 2014

Study Record Updates

• Last Update Posted (Actual): May 21, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Purpura fulminans, Sepsis, Epidemiology, Morbidity, Therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Hemorrhage; Systemic Inflammatory Response Syndrome; Inflammation; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Sepsis; Purpura; Toxemia; Purpura Fulminans
• Other Study ID Numbers: ZKSJ0065

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO