<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02238795</url>
  </required_header>
  <id_info>
    <org_study_id>ZKSJ0065</org_study_id>
    <nct_id>NCT02238795</nct_id>
  </id_info>
  <brief_title>Sepsis-Associated Purpura Fulminans International Registry - Europe</brief_title>
  <acronym>SAPFIRE</acronym>
  <official_title>Sepsis-Associated Purpura Fulminans International Registry - Europe</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jena University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ludwig-Maximilians - University of Munich</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Tuebingen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital of Cologne</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Essen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Insel Gruppe AG, University Hospital Bern</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hannover Medical School</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Basel, Switzerland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Evangelisches Krankenhaus Bielefeld gGmbH</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Universitätsklinikum Hamburg-Eppendorf</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Jena University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Sepsis-associated Purpura fulminans (SAPF) is a rare life-threatening condition. It is&#xD;
      characterized by multiple skin lesions which rapidly progress to necrosis and gangrene. SAPF&#xD;
      is a manifestation of widespread clot formation in small blood vessels which emerges&#xD;
      secondarily to severe bacterial and viral infections. The clinical presentation of SAPF is&#xD;
      dominated by symptoms of severe sepsis and multiple organ failure which are further&#xD;
      aggravated by the massive skin lesions.&#xD;
&#xD;
      At present, there are no evidence-based guidelines for the medical management of SAPF. With&#xD;
      numerous therapeutic approaches in use, there are no consistent comparisons of their&#xD;
      efficacy. Altered role of causal pathogens following the introduction of meningococcal and&#xD;
      pneumococcal prophylactic vaccines also remains to be investigated.&#xD;
&#xD;
      The goal of the registry is comprehensive collection and evaluation of information concerning&#xD;
      the epidemiology, morbidity, therapy and outcome of SAPF.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Purpura fulminans is the clinical manifestation of disseminated thrombosis in dermal and&#xD;
      systemic microcirculation. This rare disease is frequently associated with multiple organ&#xD;
      failure and represents a life-threatening condition with mortality exceeding 50 %. In the&#xD;
      vast proportion of cases, the condition has been shown to emerge secondary to acquired&#xD;
      Protein C deficiency associated with severe sepsis, mostly of meningococcal or pneumococcal&#xD;
      origin.&#xD;
&#xD;
      A consistent therapeutic approach to sepsis-associated Purpura fulminans (SAPF) has not been&#xD;
      established yet. With exaggerated pro-coagulant activity being confirmed as the key&#xD;
      pathogenic aspect, several treatment modalities aiming at the balance restoration in the&#xD;
      coagulation cascade have been considered.&#xD;
&#xD;
      SAPF causality might have been substantially altered in the wake of widespread meningococcal&#xD;
      and pneumococcal vaccination. There are neither evidence-based treatment guidelines nor&#xD;
      comparative evaluation of the efficacy of different therapeutic approaches.&#xD;
&#xD;
      The present registry aims at a) large-scale data accumulation and comprehensive evaluation of&#xD;
      the incidence, causality and current treatment strategies of SAPF, b) comparative assessment&#xD;
      of treatment strategies including or not including protein C supplementation c)&#xD;
      identification of patient subgroups of particular eligibility for Protein C treatment, as&#xD;
      judged by established criteria of disease severity assessment, d) feedback of aggregated data&#xD;
      to registry contributors, thus permitting quality management and standard updates, e)&#xD;
      dissemination of data evaluation summaries and recommendations for the use of Protein C&#xD;
      formulations in clinical routine, f) elaboration of a framework for SAPF treatment&#xD;
      recommendations and guidelines.&#xD;
&#xD;
      The registry comprises prospective, multicentric open-label data collection on the current&#xD;
      state of incidence and management of SAPF, regardless of the etiopathogenic background. It&#xD;
      will include comprehensive records on diagnosis, morbidity and management of SAPF, supplied&#xD;
      in the form of electronic case report forms (eCRFs) by the participating centers over a&#xD;
      period of three years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2016</start_date>
  <completion_date type="Actual">September 30, 2020</completion_date>
  <primary_completion_date type="Actual">September 30, 2020</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>3 Months</target_duration>
  <primary_outcome>
    <measure>Mortality</measure>
    <time_frame>during hospital stay (estimated up to 3 months)</time_frame>
    <description>All-cause in-hospital mortality assessed at day 1, day 3, day 5, and day 7, ICU and hospital discharge</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Morbidity</measure>
    <time_frame>7 days</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Extent and severity of Purpura fulminans lesions</measure>
    <time_frame>7 days</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Purpura fulminans related surgery</measure>
    <time_frame>during hospital stay (estimated up to 3 months)</time_frame>
    <description>Surgical interventions for irreversible purpura damage (debridement, fasciotomy, amputations)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Invasive pathogen</measure>
    <time_frame>during hospital stay (estimated up to 3 months)</time_frame>
    <description>Phenotyping of the microbial pathogen and definition of its antibiotic resistance, at hospital discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Site of primary infection</measure>
    <time_frame>during hospital stay (estimated up to 3 months)</time_frame>
    <description>Organ/system primarily affected by microbial infection, at hospital discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of ICU stay</measure>
    <time_frame>during ICU stay (estimated up to 3 months)</time_frame>
    <description>Duration of hospitalization in an ICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hospital stay</measure>
    <time_frame>during hospital stay (estimated up to 3 months)</time_frame>
    <description>Duration of hospitalization in an ICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory indices of organ dysfunction</measure>
    <time_frame>7 days</time_frame>
    <description>Plasma levels of glucose, lactate and creatine kinase inclusion, day 1, day 3, day 5, and day 7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory parameters</measure>
    <time_frame>7 days</time_frame>
    <description>Plasma concentrations of C-reactive protein, procalcitonin and interleukin-6 inclusion, day 1, day 3, day 5, and day 7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation parameters</measure>
    <time_frame>7 days</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematological parameters</measure>
    <time_frame>7 days</time_frame>
    <description>Recording of white blood cell count (WBC) counts, platelet counts and hemoglobin levels at inclusion, day 1, day 3, day 5, and day 7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse drug reactions</measure>
    <time_frame>during hospital stay (estimated up to 3 months)</time_frame>
    <description>Adverse Drug Reaction related to specific PF treatment (administration of anticoagulants/blood products) at hospital discharge</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Antimicrobial therapy</measure>
    <time_frame>during ICU stay (estimated up to 3 months)</time_frame>
    <description>Recording of type, dosis and duration of antibiotic use at inclusion, day 1, day 3, day 5, day 7, and ICU discharge</description>
  </other_outcome>
  <other_outcome>
    <measure>Vasopressors</measure>
    <time_frame>during ICU stay (estimated up to 3 months)</time_frame>
    <description>Cumulative doses of vasopressor drugs at inclusion, day 1, day 3, day 5, day 7, and at ICU discharge</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood products</measure>
    <time_frame>during ICU stay (estimated up to 3 months)</time_frame>
    <description>Type and cumulative dose of blood products used (RBC, platelets), at day 1, day 3, day 5, day 7, and at ICU discharge</description>
  </other_outcome>
  <other_outcome>
    <measure>Anticoagulant treatment</measure>
    <time_frame>during ICU stay (estimated up to 3 months)</time_frame>
    <description>Type and cumulative dose of anticoagulant therapy at inclusion, day 1, day 3, day 5, and day , and ICU discharge</description>
  </other_outcome>
  <other_outcome>
    <measure>Adjunctive therapy</measure>
    <time_frame>7 days</time_frame>
    <description>Type and cumulative doses of supportive therapy (corticoids, immunoglobulins, plasmapheresis, hemofiltration etc.)</description>
  </other_outcome>
  <other_outcome>
    <measure>Duration of mechanical ventilation</measure>
    <time_frame>during ICU stay (estimated up to 3 months)</time_frame>
    <description>Overall duration of use of mechanical ventilation (hours)</description>
  </other_outcome>
  <other_outcome>
    <measure>Need of renal replacement therapy</measure>
    <time_frame>during ICU stay (estimated up to 3 months)</time_frame>
    <description>Type and duration (hours) of renal replacement therapy at day 1, day 3, day 5, and day 7, and ICU discharge</description>
  </other_outcome>
  <other_outcome>
    <measure>ECMO or other circulatory support systems</measure>
    <time_frame>during ICU stay (estimated up to 3 months)</time_frame>
    <description>Use of ECMO or other circulatory support Systems, day 1, day 3, day 5, and day 7, and ICU discharge</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">28</enrollment>
  <condition>Sepsis</condition>
  <arm_group>
    <arm_group_label>Purpura fulminans</arm_group_label>
    <description>Patients diagnosed with Purpura fulminans in association with sepsis</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood plasma&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients diagnosed with sepsis-associated Purpura fulminans&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of sepsis and Purpura fulminans&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Premature neonates (below gestational age of 36 weeks)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Frank M Brunkhorst, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Center for Clinical Studies, Jena University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Jena, Klinik für Anästhesiologie und Intensivmedizin</name>
      <address>
        <city>Jena</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Jena, Klinik für Kinder- und Jugendmedizin</name>
      <address>
        <city>Jena</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der Universität München</name>
      <address>
        <city>Munich</city>
        <zip>80337</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>http://www.sapfire-registry.org/</url>
    <description>Registry website</description>
  </link>
  <reference>
    <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.</citation>
    <PMID>25348051</PMID>
  </reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>September 10, 2014</study_first_submitted>
  <study_first_submitted_qc>September 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <last_update_submitted>February 18, 2021</last_update_submitted>
  <last_update_submitted_qc>February 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Purpura fulminans, Sepsis, Epidemiology, Morbidity, Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
    <mesh_term>Purpura</mesh_term>
    <mesh_term>Purpura Fulminans</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>October 8, 2021</submitted>
    <returned>November 5, 2021</returned>
    <submitted>January 13, 2022</submitted>
    <returned>March 15, 2022</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02238795
org study id: ZKSJ0065
nct id: NCT02238795
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
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.
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.
observational model: Case-Only
time perspective: Prospective
measure: Mortality
time frame: during hospital stay (estimated up to 3 months)
description: All-cause in-hospital mortality assessed at day 1, day 3, day 5, and day 7, ICU and hospital discharge
measure: Morbidity
time frame: 7 days
description: 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
measure: Extent and severity of Purpura fulminans lesions
time frame: 7 days
description: 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
measure: Purpura fulminans related surgery
time frame: during hospital stay (estimated up to 3 months)
description: Surgical interventions for irreversible purpura damage (debridement, fasciotomy, amputations)
measure: Invasive pathogen
time frame: during hospital stay (estimated up to 3 months)
description: Phenotyping of the microbial pathogen and definition of its antibiotic resistance, at hospital discharge
measure: Site of primary infection
time frame: during hospital stay (estimated up to 3 months)
description: Organ/system primarily affected by microbial infection, at hospital discharge
measure: Duration of ICU stay
time frame: during ICU stay (estimated up to 3 months)
description: Duration of hospitalization in an ICU
measure: Duration of hospital stay
time frame: during hospital stay (estimated up to 3 months)
description: Duration of hospitalization in an ICU
measure: Laboratory indices of organ dysfunction
time frame: 7 days
description: Plasma levels of glucose, lactate and creatine kinase inclusion, day 1, day 3, day 5, and day 7
measure: Inflammatory parameters
time frame: 7 days
description: Plasma concentrations of C-reactive protein, procalcitonin and interleukin-6 inclusion, day 1, day 3, day 5, and day 7
measure: Coagulation parameters
time frame: 7 days
description: 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
measure: Hematological parameters
time frame: 7 days
description: Recording of white blood cell count (WBC) counts, platelet counts and hemoglobin levels at inclusion, day 1, day 3, day 5, and day 7
measure: Adverse drug reactions
time frame: during hospital stay (estimated up to 3 months)
description: Adverse Drug Reaction related to specific PF treatment (administration of anticoagulants/blood products) at hospital discharge
measure: Antimicrobial therapy
time frame: during ICU stay (estimated up to 3 months)
description: Recording of type, dosis and duration of antibiotic use at inclusion, day 1, day 3, day 5, day 7, and ICU discharge
measure: Vasopressors
time frame: during ICU stay (estimated up to 3 months)
description: Cumulative doses of vasopressor drugs at inclusion, day 1, day 3, day 5, day 7, and at ICU discharge
measure: Blood products
time frame: during ICU stay (estimated up to 3 months)
description: Type and cumulative dose of blood products used (RBC, platelets), at day 1, day 3, day 5, day 7, and at ICU discharge
measure: Anticoagulant treatment
time frame: during ICU stay (estimated up to 3 months)
description: Type and cumulative dose of anticoagulant therapy at inclusion, day 1, day 3, day 5, and day , and ICU discharge
measure: Adjunctive therapy
time frame: 7 days
description: Type and cumulative doses of supportive therapy (corticoids, immunoglobulins, plasmapheresis, hemofiltration etc.)
measure: Duration of mechanical ventilation
time frame: during ICU stay (estimated up to 3 months)
description: Overall duration of use of mechanical ventilation (hours)
measure: Need of renal replacement therapy
time frame: during ICU stay (estimated up to 3 months)
description: Type and duration (hours) of renal replacement therapy at day 1, day 3, day 5, and day 7, and ICU discharge
measure: ECMO or other circulatory support systems
time frame: during ICU stay (estimated up to 3 months)
description: Use of ECMO or other circulatory support Systems, day 1, day 3, day 5, and day 7, and ICU discharge
arm group label: Purpura fulminans
description: Patients diagnosed with Purpura fulminans in association with sepsis
Blood plasma
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Frank M Brunkhorst, MD
role: Study Chair
affiliation: Center for Clinical Studies, Jena University Hospital
facility: 
facility: 
facility: 
country: Germany
url: http://www.sapfire-registry.org/
description: Registry website
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.
PMID: 25348051
responsible party type: Sponsor
mesh term: Sepsis
mesh term: Toxemia
mesh term: Purpura
mesh term: Purpura Fulminans
sharing ipd: No
submitted: October 8, 2021
returned: November 5, 2021
submitted: January 13, 2022
returned: March 15, 2022