Sepsis-Associated Purpura Fulminans International Registry - Europe

Sepsis Clinical Trial

— SAPFIRE  

Official title:

Sepsis-Associated Purpura Fulminans International Registry - Europe

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02238795
• Other study ID #: ZKSJ0065
• Status: Completed
• Start date: April 2016
• Est. completion date: September 30, 2020

Study information

• Verified date: February 2021
• Source: Jena University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: September 30, 2020
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Diagnosis of sepsis and Purpura fulminans

• Signed informed consent

Exclusion Criteria:

• Premature neonates (below gestational age of 36 weeks)

Related Conditions & MeSH terms

• Purpura
• Purpura Fulminans
• Sepsis
• Toxemia

Locations

Country	Name	City	State
Germany	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

Sponsors (11)

Lead Sponsor	Collaborator
Jena University Hospital	Evangelisches Krankenhaus Bielefeld gGmbH, Hannover Medical School, Ludwig-Maximilians - University of Munich, Medical University of Vienna, Universitätsklinikum Hamburg-Eppendorf, University Hospital Inselspital, Berne, University Hospital of Cologne, University Hospital Tuebingen, University Hospital, Basel, Switzerland, University Hospital, Essen

Country where clinical trial is conducted

Germany, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Antimicrobial therapy	Recording of type, dosis and duration of antibiotic use at inclusion, day 1, day 3, day 5, day 7, and ICU discharge	during ICU stay (estimated up to 3 months)
Other	Vasopressors	Cumulative doses of vasopressor drugs at inclusion, day 1, day 3, day 5, day 7, and at ICU discharge	during ICU stay (estimated up to 3 months)
Other	Blood products	Type and cumulative dose of blood products used (RBC, platelets), at day 1, day 3, day 5, day 7, and at ICU discharge	during ICU stay (estimated up to 3 months)
Other	Anticoagulant treatment	Type and cumulative dose of anticoagulant therapy at inclusion, day 1, day 3, day 5, and day , and ICU discharge	during ICU stay (estimated up to 3 months)
Other	Adjunctive therapy	Type and cumulative doses of supportive therapy (corticoids, immunoglobulins, plasmapheresis, hemofiltration etc.)	7 days
Other	Duration of mechanical ventilation	Overall duration of use of mechanical ventilation (hours)	during ICU stay (estimated up to 3 months)
Other	Need of renal replacement therapy	Type and duration (hours) of renal replacement therapy at day 1, day 3, day 5, and day 7, and ICU discharge	during ICU stay (estimated up to 3 months)
Other	ECMO or other circulatory support systems	Use of ECMO or other circulatory support Systems, day 1, day 3, day 5, and day 7, and ICU discharge	during ICU stay (estimated up to 3 months)
Primary	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	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
Secondary	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
Secondary	Purpura fulminans related surgery	Surgical interventions for irreversible purpura damage (debridement, fasciotomy, amputations)	during hospital stay (estimated up to 3 months)
Secondary	Invasive pathogen	Phenotyping of the microbial pathogen and definition of its antibiotic resistance, at hospital discharge	during hospital stay (estimated up to 3 months)
Secondary	Site of primary infection	Organ/system primarily affected by microbial infection, at hospital discharge	during hospital stay (estimated up to 3 months)
Secondary	Duration of ICU stay	Duration of hospitalization in an ICU	during ICU stay (estimated up to 3 months)
Secondary	Duration of hospital stay	Duration of hospitalization in an ICU	during hospital stay (estimated up to 3 months)
Secondary	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
Secondary	Inflammatory parameters	Plasma concentrations of C-reactive protein, procalcitonin and interleukin-6 inclusion, day 1, day 3, day 5, and day 7	7 days
Secondary	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
Secondary	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
Secondary	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)

External Links

•   Registry website