Sepsis-Associated Purpura Fulminans International Registry - Europe

Study Overview
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Brief Summary
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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
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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.

Official Title
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Sepsis-Associated Purpura Fulminans International Registry - Europe

Conditions
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Sepsis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of sepsis and Purpura fulminans Signed informed consent Exclusion Criteria: Premature neonates (below gestational age of 36 weeks)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Purpura fulminans<br>Patients diagnosed with Purpura fulminans in association with sepsis | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | All-cause in-hospital mortality assessed at day 1, day 3, day 5, and day 7, ICU and hospital discharge | during hospital stay (estimated up to 3 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity | Changes in signs of organ dysfunction - sequential organ failure assessment score (SOFA), or paediatric logistic organ dysfunction scores (PELOD), at inclusion, day 1, day 3, day 5, and day 7 | 7 days | 
| Extent and severity of Purpura fulminans lesions | Pictorial registration of localization (body parts) and severity (4 grades) of cutaneous lesions at intervals at inclusion, day 1, day 3, day 5, and day 7 | 7 days | 
| Purpura fulminans related surgery | Surgical interventions for irreversible purpura damage (debridement, fasciotomy, amputations) | during hospital stay (estimated up to 3 months) | 
| Invasive pathogen | Phenotyping of the microbial pathogen and definition of its antibiotic resistance, at hospital discharge | during hospital stay (estimated up to 3 months) | 
| Site of primary infection | Organ/system primarily affected by microbial infection, at hospital discharge | during hospital stay (estimated up to 3 months) | 
| Duration of ICU stay | Duration of hospitalization in an ICU | during ICU stay (estimated up to 3 months) | 
| Duration of hospital stay | Duration of hospitalization in an ICU | during hospital stay (estimated up to 3 months) | 
| Laboratory indices of organ dysfunction | Plasma levels of glucose, lactate and creatine kinase inclusion, day 1, day 3, day 5, and day 7 | 7 days | 
| Inflammatory parameters | Plasma concentrations of C-reactive protein, procalcitonin and interleukin-6 inclusion, day 1, day 3, day 5, and day 7 | 7 days | 
| Coagulation parameters | Recording of plasma concentrations of prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimers, thrombin-antithrombin complex, protein C activity, antithrombin III activity inclusion, day 1, day 3, day 5, and day 7 | 7 days | 
| Hematological parameters | Recording of white blood cell count (WBC) counts, platelet counts and hemoglobin levels at inclusion, day 1, day 3, day 5, and day 7 | 7 days | 
| Adverse drug reactions | Adverse Drug Reaction related to specific PF treatment (administration of anticoagulants/blood products) at hospital discharge | during hospital stay (estimated up to 3 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Purpura fulminans, Sepsis, Epidemiology, Morbidity, Therapy