Clinical trial NCT02238795: Sepsis-Associated Purpura Fulminans International Registry - Europe
Official title: Sepsis-Associated Purpura Fulminans International Registry - Europe
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis
Keywords: Purpura fulminans, Sepsis, Epidemiology, Morbidity, Therapy
Lead sponsor: Jena University Hospital
Sponsor class: OTHER
Collaborators: name: Ludwig-Maximilians - University of Munich
name: Medical University of Vienna
name: University Hospital Tuebingen
name: University Hospital of Cologne
name: University Hospital, Essen
name: Insel Gruppe AG, University Hospital Bern
name: Hannover Medical School
name: University Hospital, Basel, Switzerland
name: Evangelisches Krankenhaus Bielefeld gGmbH
name: Universitätsklinikum Hamburg-Eppendorf
First posted: 2014-09-12
Enrollment: 28
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with sepsis-associated Purpura fulminans

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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of sepsis and Purpura fulminans
* Signed informed consent

Exclusion Criteria:

* Premature neonates (below gestational age of 36 weeks)

Primary outcomes:
measure: Mortality
timeFrame: during hospital stay (estimated up to 3 months)
Secondary outcomes:
measure: Hospital Stay
timeFrame: duration of hospital stay, up to 3 months
measure: Extent and Severity of Purpura Fulminans Lesions
timeFrame: 7 days
measure: Mean Total Sepsis-related Organ Failure Assessment (SOFA) Score
timeFrame: day 7
measure: Protein C
timeFrame: until day 7
measure: Duration of ICU Stay
timeFrame: during ICU stay (estimated up to 3 months)
measure: Adverse Drug Reactions: Visual Nerve Damage
timeFrame: during hospital stay (estimated up to 3 months)
measure: Adverse Drug Reaction: Bleeding
timeFrame: during ICU stay
measure: Adverse Drug Reaction: Thrombotic Events
timeFrame: during ICU stay
measure: Amputation
timeFrame: during ICU stay
Other outcomes:
measure: Vasopressor Days
timeFrame: during ICU stay (estimated up to 3 months)
measure: Ventilator-free Days
timeFrame: during ICU stay (estimated up to 3 months)
measure: Renal Replacement Therapy
timeFrame: during ICU stay (estimated up to 3 months)
Locations:
city: Jena
country: Germany
facility: University Hospital Jena, Klinik für Anästhesiologie und Intensivmedizin
city: Jena
country: Germany
facility: University Hospital Jena, Klinik für Kinder- und Jugendmedizin
city: Munich
country: Germany
facility: Klinikum der Universität München
Study officials:
affiliation: Center for Clinical Studies, Jena University Hospital
name: Frank M Brunkhorst, MD
role: STUDY_CHAIR
References:
citation: 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.