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The purpose of this study is to compare the safety and efficacy of the antibiotic tigecycline with other antibiotics, ampicillin-sulbactam, and amoxicillin-clavulanate in the treatment of a complicated skin and/or skin structure infection (cSSSI).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | Arm 1: Tigecycline |
|
| 2 | Active Comparator | Arm 2: Ampicillin-Sulbactam or Amoxicillin-Clavulanate plus or minus a glycopeptide |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tigecycline | Drug | Treatment A: Tigecycline every 12 hours intravenous (IV) (an initial dose of 100 mg followed by 50 mg every 12 hours) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Clinically Evaluable (CE) Patients With Clinical Response of Cure at the Test-of-cure (TOC) Visit | Investigator assigned clinical response of cure of the cSSSI defined as: resolution of all clinical signs and symptoms of infection (healing of chronic underlying skin ulcer not required) or improvement of signs or symptoms of the infection to such an extent that no further antibacterial therapy was necessary. CE population were those who completed TOC assessment of cure or failure (but not indeterminate) or, in case of premature discontinuation due to lack of efficacy, had completed end of treatment assessment such that assessment of clinical response could be made. | up to 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Microbiologically Evaluable Patients With Clinical Response of Cure at the Test-of-cure (TOC) Visit | Investigator assigned clinical response of cure of the cSSSI defined as: resolution of all clinical signs and symptoms of infection (healing of chronic underlying skin ulcer not required) or improvement of signs or symptoms of the infection to such an extent that no further antibacterial therapy was necessary. ME population were subjects who were CE and had baseline culture with at least 1 identified isolate that was susceptible to study drug and comparator. TOC performed 8-50 days after last dose of study drug. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Wyeth is now a wholly owned subsidiary of Pfizer | Study Director |
| Trial Manager | For Hong Kong: medinfo@wyeth.com | Principal Investigator |
| Trial Manager | For South Africa: ZAFinfo@wyeth.com | Principal Investigator |
| Trial Manager | For Taiwan: medinfo@wyeth.com | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Scottsdale | Arizona | 85251 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23145952 | Derived | Matthews P, Alpert M, Rahav G, Rill D, Zito E, Gardiner D, Pedersen R, Babinchak T, McGovern PC; Tigecycline 900 cSSSI Study Group. A randomized trial of tigecycline versus ampicillin-sulbactam or amoxicillin-clavulanate for the treatment of complicated skin and skin structure infections. BMC Infect Dis. 2012 Nov 12;12:297. doi: 10.1186/1471-2334-12-297. |
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Patients were screened according to the inclusion/exclusion criteria. Once informed consent was obtained, the patient was enrolled into the study and assigned a randomization number and a treatment regimen.
Patients were recruited worldwide from September 2006 to August 2008.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tigecycline | Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours) |
| FG001 | Ampicillin-Sulbactam or Amoxicillin-Clavulanate | Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Randomization |
|
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| ampicillin-sulbactam | Drug | Ampicillin-sulbactam: 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (3 g ampicillin plus 1 g sulbactam) intravenous (IV) every 6 hrs or Amoxicillin-clavulanate: 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hrs. A glycopeptide antibiotic (either vancomycin 1 g IV every 12 hrs or teicoplanin IV loading dose of 400 mg the first day followed by a maintenance dose of 200 mg daily) may be added to the aminopenicillin/betalactamase inhibitor regimen if infection with methicillin-resistant staphylococcus aureus (MRSA) is suspected or confirmed within the first 72 hrs of enrollment. If culture results fail to show a resistant organism, use of the glycopeptide may be discontinued. |
|
| up to 6 weeks |
| Number of Microbiologically Evaluable Patients by Microbiologic Response at Test-of-Cure (TOC) Visit | Microbiological response assessed at patient level. Eradication=baseline isolate not present in repeat culture from the original infection site; Presumed Eradication=clinical response of cure precluded the availability of a specimen for culture; Persistence=baseline isolate present in repeat culture from the original infection site; Presumed Persistence=culture data not available for patients with a clinical response of failure; Superinfection=culture from the primary infection site had new pathogen not identified as a baseline isolate and clinical response was failure. | up to 6 weeks |
| Minimum Inhibitory Concentration (MIC) 50 and 90 by Baseline Isolate | In vitro activity of the study drugs against a range of pathogenic bacteria that cause complicated skin and skin structure infection (cSSSI) were analyzed using MIC. MIC 50 and MIC 90 are the lowest concentrations of a drug that inhibit the growth of 50% and 90% of a microorganism, respectively. TOC performed 8-50 days after last dose of study drug. | up to 6 weeks |
| Inpatient Healthcare Resource Utilization on or Before Test-of-Cure - Number of Patients | Healthcare resource utilization assessment included intensive care unit (ICU) and non-ICU inpatient hospitalization. TOC performed 8-50 days after last dose of study drug. | up to 6 weeks |
| Jonesboro |
| Arkansas |
| 72401 |
| United States |
| Chula Vista | California | 91911 | United States |
| Mission Viejo | California | 92691 | United States |
| National City | California | 91950 | United States |
| Denver | Colorado | 80218 | United States |
| Washington D.C. | District of Columbia | 20017 | United States |
| Washington D.C. | District of Columbia | 20037 | United States |
| Orlando | Florida | 32803 | United States |
| Vero Beach | Florida | 32960 | United States |
| Fort Eisenhower | Georgia | 30905 | United States |
| Idaho Falls | Idaho | 83404 | United States |
| Decatur | Illinois | 62526 | United States |
| Naperville | Illinois | 60540 | United States |
| Springfield | Illinois | 62702 | United States |
| Topeka | Kansas | 66606 | United States |
| Cambridge | Massachusetts | 02139 | United States |
| Worcester | Massachusetts | 01655 | United States |
| Detroit | Michigan | 48202 | United States |
| Lincoln | Nebraska | 68510 | United States |
| Hackensack | New Jersey | 07601 | United States |
| Neptune City | New Jersey | 07754 | United States |
| Buffalo | New York | 14215 | United States |
| Elmira | New York | 14905 | United States |
| New Hyde Park | New York | 11040 | United States |
| Columbus | Ohio | 43214 | United States |
| Lima | Ohio | 45801 | United States |
| Lansdale | Pennsylvania | 19446 | United States |
| Philadelphia | Pennsylvania | 19140 | United States |
| Fort Worth | Texas | 76104 | United States |
| Houston | Texas | 77026 | United States |
| Winnipeg | Manitoba | R3A 1R9 | Canada |
| Chicoutimi | Quebec | G7H 5H6 | Canada |
| Montreal | Quebec | H1T 2M4 | Canada |
| Québec | Quebec | G1V 4G5 | Canada |
| Sherbrooke | Quebec | J1H 5N4 | Canada |
| Trois-Rivières | Quebec | G8Z 3R9 | Canada |
| Saskatoon | Saskatchewan | S7N 0W8 | Canada |
| Hong Kong | Hong Kong |
| Ramat Gan | 52621 | Israel |
| Beirut | 110 32090 | Lebanon |
| Pulau Pinang | 10990 | Malaysia |
| Manila | 1000 | Philippines |
| Manila | 1014 | Philippines |
| Singapore | 169608 | Singapore |
| Cape Town | 7531 | South Africa |
| Gauteng | 0181 | South Africa |
| KZ-Natal | 3610 | South Africa |
| Mpumalanga | 1050 | South Africa |
| Daejeon | 301-721 | South Korea |
| Incheon | 405-760 | South Korea |
| Seoul | 120-752 | South Korea |
| Seoul | 133-791 | South Korea |
| Taipei | 220 | Taiwan |
| Bangkok | 10330 | Thailand |
| Bangkok | 10400 | Thailand |
| Bangkok | 10700 | Thailand |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Baseline Participants |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Tigecycline | Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours) |
| BG001 | Ampicillin-Sulbactam or Amoxicillin-Clavulanate | Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Clinically Evaluable (CE) Patients With Clinical Response of Cure at the Test-of-cure (TOC) Visit | Investigator assigned clinical response of cure of the cSSSI defined as: resolution of all clinical signs and symptoms of infection (healing of chronic underlying skin ulcer not required) or improvement of signs or symptoms of the infection to such an extent that no further antibacterial therapy was necessary. CE population were those who completed TOC assessment of cure or failure (but not indeterminate) or, in case of premature discontinuation due to lack of efficacy, had completed end of treatment assessment such that assessment of clinical response could be made. | Clinically Evaluable (CE): Patients with cSSSI, no Pseudomonas aeruginosa as sole baseline isolate, met major inclusion/exclusion criteria, ≤24 hrs antibiotics pre-baseline, had ≥4 days of study drug, compliant with therapy. Excludes indeterminates. | Posted | Sep 2009 | Number | participants | up to 6 weeks |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Microbiologically Evaluable Patients With Clinical Response of Cure at the Test-of-cure (TOC) Visit | Investigator assigned clinical response of cure of the cSSSI defined as: resolution of all clinical signs and symptoms of infection (healing of chronic underlying skin ulcer not required) or improvement of signs or symptoms of the infection to such an extent that no further antibacterial therapy was necessary. ME population were subjects who were CE and had baseline culture with at least 1 identified isolate that was susceptible to study drug and comparator. TOC performed 8-50 days after last dose of study drug. | Microbiologically Evaluable patients:Clinically Evaluable (CE) patients who had baseline culture with ≥1 identified pathogen susceptible to both study drugs (ie, the pathogen is susceptible to tigecycline and comparator). Excludes indeterminates. | Posted | Sep 2009 | Number | participants | up to 6 weeks |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Microbiologically Evaluable Patients by Microbiologic Response at Test-of-Cure (TOC) Visit | Microbiological response assessed at patient level. Eradication=baseline isolate not present in repeat culture from the original infection site; Presumed Eradication=clinical response of cure precluded the availability of a specimen for culture; Persistence=baseline isolate present in repeat culture from the original infection site; Presumed Persistence=culture data not available for patients with a clinical response of failure; Superinfection=culture from the primary infection site had new pathogen not identified as a baseline isolate and clinical response was failure. | Microbiologically Evaluable patients:CE patients who had baseline culture with ≥1 identified pathogen susceptible to both study drugs (ie, the pathogen is susceptible to tigecycline and comparator). TOC performed 8-50 days after last dose of study drug. | Posted | Sep 2009 | Number | participants | up to 6 weeks |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Minimum Inhibitory Concentration (MIC) 50 and 90 by Baseline Isolate | In vitro activity of the study drugs against a range of pathogenic bacteria that cause complicated skin and skin structure infection (cSSSI) were analyzed using MIC. MIC 50 and MIC 90 are the lowest concentrations of a drug that inhibit the growth of 50% and 90% of a microorganism, respectively. TOC performed 8-50 days after last dose of study drug. | m-mITT: Patients with ≥1 dose of study drug, had cSSSI and baseline isolate from infection site / blood. MIC reported for isolates present in ≥10 m-mITT patients. In the categories below "n" is the actual number of isolates used to caluculate the MIC 50 and MIC 90. | Posted | Sep 2009 | Number | mcg/mL | up to 6 weeks |
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| Secondary | Inpatient Healthcare Resource Utilization on or Before Test-of-Cure - Number of Patients | Healthcare resource utilization assessment included intensive care unit (ICU) and non-ICU inpatient hospitalization. TOC performed 8-50 days after last dose of study drug. | All patients who received at least 1 dose of study article. | Posted | Sep 2009 | Number | participants | up to 6 weeks |
|
|
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This data represents the number of times a given adverse event was reported. The given participant may have experienced more than one adverse event. We are looking at the frequency of adverse events based on event and not by participant.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tigecycline | Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours) | 38 | 268 | 396 | 268 | ||
| EG001 | Ampicillin-Sulbactam or Amoxicillin-Clavulanate | Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours. | 29 | 263 | 241 | 263 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis | General disorders | Non-systematic Assessment |
| ||
| Infection | General disorders | Non-systematic Assessment |
| ||
| Abscess | General disorders | Non-systematic Assessment |
| ||
| Chest pain | General disorders | Non-systematic Assessment |
| ||
| General physical health deterioration | General disorders | Non-systematic Assessment |
| ||
| Asthenia | General disorders | Non-systematic Assessment |
| ||
| Carcinoma | General disorders | Non-systematic Assessment |
| ||
| Fever | General disorders | Non-systematic Assessment |
| ||
| Generalized edema | General disorders | Non-systematic Assessment |
| ||
| Overdose | General disorders | Non-systematic Assessment |
| ||
| Retroperitoneal hemorrhage | General disorders | Non-systematic Assessment |
| ||
| Sepsis | General disorders | Non-systematic Assessment |
| ||
| Septic shock | General disorders | Non-systematic Assessment |
| ||
| Traumatic hematoma | General disorders | Non-systematic Assessment |
| ||
| Heart arrest | Cardiac disorders | Non-systematic Assessment |
| ||
| Pulmonary embolus | Vascular disorders | Non-systematic Assessment |
| ||
| Deep vein thrombosis | Vascular disorders | Non-systematic Assessment |
| ||
| Myocardial infarct | Cardiac disorders | Non-systematic Assessment |
| ||
| Occlusion | Vascular disorders | Non-systematic Assessment |
| ||
| Ventricular tachycardia | Cardiac disorders | Non-systematic Assessment |
| ||
| Cholecystitis | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Esophageal hemorrhage | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Gastrointestinal hemorrhage | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Hepatic failure | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Liver function tests abnormal | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Peptic ulcer | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Stomach ulcer | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Lung edema | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Carcinoma of lung | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Chronic obstructive airways disease | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Acute kidney failure | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Kidney failure | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Kidney function abnormal | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Urinary tract infection | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Dehydration | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypoglycemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Healing abnormal | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Skin necrosis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| Herpes simplex | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| Necrotising fasciitis | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Osteomyelitis | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Convulsion | Nervous system disorders | Non-systematic Assessment |
| ||
| Encephalopathy | Nervous system disorders | Non-systematic Assessment |
| ||
| International normalized ratio increased | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Dyspepsia | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Headache | General disorders | Non-systematic Assessment |
| ||
| Pain | General disorders | Non-systematic Assessment |
| ||
| Abdominal pain | General disorders | Non-systematic Assessment |
| ||
| Fever | General disorders | Non-systematic Assessment |
| ||
| Chest pain | General disorders | Non-systematic Assessment |
| ||
| Insomnia | Nervous system disorders | Non-systematic Assessment |
| ||
| Anxiety | Nervous system disorders | Non-systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Non-systematic Assessment |
| ||
| Hypokalemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Pruritus | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| Hypertension | Vascular disorders | Non-systematic Assessment |
| ||
| Anemia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| U. S. Contact Center | Wyeth | clintrialresults@wyeth.com |
| ID | Term |
|---|---|
| D017192 | Skin Diseases, Bacterial |
| D002481 | Cellulitis |
| ID | Term |
|---|---|
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D012874 | Skin Diseases, Infectious |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D013492 | Suppuration |
| D003240 | Connective Tissue Diseases |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
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| ID | Term |
|---|---|
| D000078304 | Tigecycline |
| C035444 | sultamicillin |
| ID | Term |
|---|---|
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
Not provided
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| Death |
|
| No susceptibility |
|
| Patient uncompliant |
|
| Male |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
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|
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| Participants |
|
|
|
|