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| ID | Type | Description | Link |
|---|---|---|---|
| R01HL117074-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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The primary purpose of this study is to investigate the efficacy and safety of oral antimycobacterial therapy in patients with confirmed progressive pulmonary sarcoidosis. We suspect that the CLEAR regimen will improve the absolute FVC percent predicted in chronic pulmonary sarcoidosis participants.
Primary Objective: To assess the efficacy and safety of oral CLEAR therapy in patients with confirmed progressive pulmonary sarcoidosis.
Hypothesis: The CLEAR regimen will improve the absolute FVC percent predicted in chronic pulmonary sarcoidosis participants by augmenting T cell responses through the normalization of p56Lck expression and IL-2 production.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin | Active Comparator | Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD |
|
| Placebo | Placebo Comparator | Riboflavin will be used for rifampin; encapsulated microcrystalline cellulose will be used to replace the levofloxacin, ethambutol and azithromycin. The pill count will be the same as the comparator regimen. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Levofloxacin | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Percent Predicted Absolute Forced Vital Capacity (FVC) in Participants With Pulmonary Sarcoidosis, Comparing Baseline With Performance After Completion of 16 Weeks of Therapy. | Change in percent predicted absolute forced vital capacity (FVC) in participants with pulmonary sarcoidosis, comparing baseline with performance after completion of 16 weeks of therapy. This will involve comparing sarcoidosis and placebo after 16 weeks of therapy. | Baseline to 16 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Radiographic Improvement in Sarcoidosis Lung Disease by Frontal Chest X-ray . | Radiographic improvement in sarcoidosis lung disease by frontal chest x-ray . Local investigators will score chest x-rays. | Baseline and 16 weeks |
| Six Minute Walk, Distance in Meters |
Not provided
Inclusion Criteria:
Patients with sarcoidosis as defined by the ATS/ERS/WASOG statement on sarcoidosis as defined by the clinical presentation consistent with sarcoidosis, as well as biopsy demonstrating granulomas, and no alternative for the cause of the granulomas, such as tuberculosis for at least one year prior to randomization.
Evidence of disease progression as defined by at least one of the following three criteria:
Decline of absolute percent predicted of FVC (FVC ≥45% or higher of predicted value) or DLCO of at least 5% on serial measurements (DLCO range >35%, if measured); Radiographic progression in chest imaging on side by side comparison; Change in dyspnea score, as measured by Transition Dyspnea Index (TDI); Positive peripheral immune responses to ESAT-6 as a biomarker of response to CLEAR regimen.
Possess evidence of parenchymal or nodal disease on chest radiograph.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wonder Drake, MD | Vanderbilt University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Albany Medical Center | Albany | New York | 12208 | United States | ||
| University of Cincinnati |
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446 participants were screened but only 97 participants met inclusion/exclusion and were randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin | Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin |
| FG001 | Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 5, 2018 |
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| Ethambutol |
| Drug |
|
| Azithromycin | Drug |
|
|
| Rifampin | Drug |
|
|
| Placebo | Drug | This will serve as a placebo to the antibiotics used in antimycobacterial therapy. |
|
The 6-min walk test (6 MWT) is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. |
| Baseline, 4, 8, and 16 and 24 weeks |
| Change in Oxygen Saturation | measured using pulse oximetry | Baseline, 4, 8, and 16 and 24 weeks |
| Change in Level of Dyspnea | Outcome measure if a composite | Baseline, 4, 8 and 16 weeks |
| Change in the Saint George's Respiratory Questionnaire (SGRQ) | The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in patients with diseases of airways obstruction. Scores range from 0 to 100, with higher scores indicating more limitations. A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing. | Baseline and 16 weeks |
| Fatigue Assessment Scale (FAS). | The FAS is a 10-item general fatigue questionnaire to assess fatigue. Total scores can range from 10, indicating the lowest level of fatigue, to 50, denoting the highest. | Baseline, 4, 8, 16 and 24 weeks |
| Change in the King's Sarcoidosis Questionnaire (KSQ) for the Assessment of Health Status; | The KSQ is a free, online questionnaire to be filled out by sarcoidosis patients. The questionnaire takes around 10 minutes and is split into 5 sections; general health status, lungs, medication, skin and eyes. There are 29 questions in total, however some questions may not be answered (depending on the type of sarcoidosis affected). Each question asks patients to rate how they feel about many different aspects of their life, for instance how much pain they are in or how difficult they find everyday tasks. Information provided is confidential. Results are given as a number between 1-100 with higher numbers indicating better health. | Baseline and 16 weeks |
| Adverse Events | Safety profile of regimen as evidenced by the number of adverse events | 24 weeks |
| FEV1% | FEV1% was measure pre and post 6 minute walk test | Baseline, 4, 8, and 16 and 24 weeks |
| Failure of Standard Therapy | We will assess how many subjects in either arm need escalation of their standard regimen (ie increase in prednisone) during the 16 weeks. | Baseline to 16 weeks |
| Abnormal Lab Values | Safety profile of regimen as evidenced by the number of abnormal lab values classified as Adverse Events | baseline to 16 weeks |
| Cincinnati |
| Ohio |
| 45267 |
| United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| Ohio State University | Columbus | Ohio | 43221 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| Vanderbilt University School of Medicine | Nashville | Tennessee | 37232 | United States |
Riboflavin will be used for rifampin; encapsulated microcrystalline cellulose will be used to replace the levofloxacin, ethambutol and azithromycin. The pill count will be the same as the comparator regimen. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy. |
| COMPLETED | includes those who did not complete the entire study drug regime but did complete study visits |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin | Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin |
| BG001 | Placebo | Riboflavin will be used for rifampin; encapsulated microcrystalline cellulose will be used to replace the levofloxacin, ethambutol and azithromycin. The pill count will be the same as the comparator regimen. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy. |
| 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 |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Weight | Mean | Standard Deviation | kilograms |
| |||||||||||||||
| Heart Rate | Mean | Standard Deviation | beats per minute |
| |||||||||||||||
| 6 minute walk test | The 6-min walk test (6 MWT) is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes | Mean | Standard Deviation | meters |
|
| 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 | Change in Percent Predicted Absolute Forced Vital Capacity (FVC) in Participants With Pulmonary Sarcoidosis, Comparing Baseline With Performance After Completion of 16 Weeks of Therapy. | Change in percent predicted absolute forced vital capacity (FVC) in participants with pulmonary sarcoidosis, comparing baseline with performance after completion of 16 weeks of therapy. This will involve comparing sarcoidosis and placebo after 16 weeks of therapy. | Only 43 participants in each arm completed this measure | Posted | Mean | Standard Deviation | percentage predicted absolute FVC | Baseline to 16 weeks |
|
|
| ||||||||||||||||||||||||||||
| Secondary | Radiographic Improvement in Sarcoidosis Lung Disease by Frontal Chest X-ray . | Radiographic improvement in sarcoidosis lung disease by frontal chest x-ray . Local investigators will score chest x-rays. | The outcome was not completed due to lack of funds for radiology services. | Posted | Baseline and 16 weeks |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Six Minute Walk, Distance in Meters | The 6-min walk test (6 MWT) is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. | Week 24 assessment was optional. Not all participants completed the 6 minute walk test. | Posted | Mean | Standard Error | meters | Baseline, 4, 8, and 16 and 24 weeks |
|
| |||||||||||||||||||||||||||||
| Secondary | Change in Oxygen Saturation | measured using pulse oximetry | not all participants completed the measure and it was not recorded at week 24 | Posted | Mean | Standard Deviation | percentage of oxygen saturation | Baseline, 4, 8, and 16 and 24 weeks |
|
| |||||||||||||||||||||||||||||
| Secondary | Change in Level of Dyspnea | Outcome measure if a composite | this measure was not administered | Posted | Baseline, 4, 8 and 16 weeks |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Change in the Saint George's Respiratory Questionnaire (SGRQ) | The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in patients with diseases of airways obstruction. Scores range from 0 to 100, with higher scores indicating more limitations. A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing. | questionnaire was only administered at baseline and 16 weeks and not all participants completed the questionnaire at week 16 | Posted | Mean | Standard Error | score on a scale | Baseline and 16 weeks |
|
| |||||||||||||||||||||||||||||
| Secondary | Fatigue Assessment Scale (FAS). | The FAS is a 10-item general fatigue questionnaire to assess fatigue. Total scores can range from 10, indicating the lowest level of fatigue, to 50, denoting the highest. | The FAS was not administered to participants. | Posted | Baseline, 4, 8, 16 and 24 weeks |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Change in the King's Sarcoidosis Questionnaire (KSQ) for the Assessment of Health Status; | The KSQ is a free, online questionnaire to be filled out by sarcoidosis patients. The questionnaire takes around 10 minutes and is split into 5 sections; general health status, lungs, medication, skin and eyes. There are 29 questions in total, however some questions may not be answered (depending on the type of sarcoidosis affected). Each question asks patients to rate how they feel about many different aspects of their life, for instance how much pain they are in or how difficult they find everyday tasks. Information provided is confidential. Results are given as a number between 1-100 with higher numbers indicating better health. | KSQ was not administered to participants. | Posted | Baseline and 16 weeks |
| |||||||||||||||||||||||||||||||||
| Secondary | Adverse Events | Safety profile of regimen as evidenced by the number of adverse events | Posted | Number | number of events | 24 weeks |
|
| |||||||||||||||||||||||||||||||
| Secondary | FEV1% | FEV1% was measure pre and post 6 minute walk test | Week 24 assessment was optional. Not all participants completed all measurements | Posted | Mean | Standard Error | Percentage of predicted FEV1 | Baseline, 4, 8, and 16 and 24 weeks |
|
| |||||||||||||||||||||||||||||
| Secondary | Failure of Standard Therapy | We will assess how many subjects in either arm need escalation of their standard regimen (ie increase in prednisone) during the 16 weeks. | Posted | Count of Participants | Participants | Baseline to 16 weeks |
|
| |||||||||||||||||||||||||||||||
| Secondary | Abnormal Lab Values | Safety profile of regimen as evidenced by the number of abnormal lab values classified as Adverse Events | Posted | Number | participants | baseline to 16 weeks |
|
|
24 weeks
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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 | Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin | Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Levofloxacin Ethambutol Azithromycin Rifampin | 0 | 49 | 4 | 49 | 24 | 49 |
| EG001 | Placebo | Riboflavin will be used for rifampin; encapsulated microcrystalline cellulose will be used to replace the levofloxacin, ethambutol and azithromycin. The pill count will be the same as the comparator regimen. Placebo: This will serve as a placebo to the antibiotics used in antimycobacterial therapy. | 0 | 48 | 3 | 48 | 16 | 48 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Neurosarcoidosis | Nervous system disorders | Systematic Assessment |
| ||
| Hypotension | Cardiac disorders | Systematic Assessment |
| ||
| Sepsis from Abcess | Infections and infestations | Systematic Assessment |
| ||
| post-operative infection | Infections and infestations | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Low Platelet count | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Low WBC Count | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| leukopenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| WBC Low | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Low WBC | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Hypotension | Cardiac disorders | Systematic Assessment |
| ||
| Loss of Hearing in Right Ear | Ear and labyrinth disorders | Systematic Assessment |
| ||
| Elevated Glucose | Endocrine disorders | Systematic Assessment |
| ||
| hypoglycemia | Endocrine disorders | Systematic Assessment |
| ||
| Worsening Glucose | Endocrine disorders | Systematic Assessment |
| ||
| hypoglycemia | Endocrine disorders | Systematic Assessment |
| ||
| elevated glucose | Endocrine disorders | Systematic Assessment |
| ||
| Floater/Blurry Vision | Eye disorders | Systematic Assessment |
| ||
| Eyes red & draining | Eye disorders | Systematic Assessment |
| ||
| diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| loss of appetite | Gastrointestinal disorders | Systematic Assessment |
| ||
| weakness | Gastrointestinal disorders | Systematic Assessment |
| ||
| nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| diarrhea/loose stool | Gastrointestinal disorders | Systematic Assessment |
| ||
| Nausea, Vomiting, Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Nauseated, Vomiting & Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| nausea, vomitting, diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Surgey (Appendectomy) | Gastrointestinal disorders | Systematic Assessment |
| ||
| Nausea & Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Diarrhea, loss of appetite, | Gastrointestinal disorders | Systematic Assessment |
| ||
| Fever, Nausea, Chills | General disorders | Systematic Assessment |
| ||
| Fever | General disorders | Systematic Assessment |
| ||
| increase in hair loss | General disorders | Systematic Assessment |
| ||
| Fatigue | General disorders | Systematic Assessment |
| ||
| Insomnia | General disorders | Systematic Assessment |
| ||
| Urine Color change | General disorders | Systematic Assessment |
| ||
| Tiredness/Fatigue | General disorders | Systematic Assessment |
| ||
| flu-like symptoms (chills, aches, fatigue) | General disorders | Systematic Assessment |
| ||
| Dehydration | General disorders | Systematic Assessment |
| ||
| Hospitalization | General disorders | Systematic Assessment |
| ||
| Right Upper Quadant Pain | General disorders | Systematic Assessment |
| ||
| fever, chills | General disorders | Systematic Assessment |
| ||
| Pruritus | General disorders | Systematic Assessment |
| ||
| Chills | General disorders | Systematic Assessment |
| ||
| Tiredness | General disorders | Systematic Assessment |
| ||
| Hard to swallow | General disorders | Systematic Assessment |
| ||
| elevated LFTs | Hepatobiliary disorders | Systematic Assessment |
| ||
| yeast infection | Infections and infestations | Systematic Assessment |
| ||
| Shingles | Infections and infestations | Systematic Assessment |
| ||
| Pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Yeast Infection, (Urine Urgency, Fever, Joint Aches) | Infections and infestations | Systematic Assessment |
| ||
| Foot Abscess | Infections and infestations | Systematic Assessment |
| ||
| Sinus Infection | Infections and infestations | Systematic Assessment |
| ||
| Reaction to medication | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Ankle Fracture | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| broken foot and fibula | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| joint pain and achiness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Joint Stiffiness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Joint pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Shoulder Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| muscle/flank/joint pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Syncope | Nervous system disorders | Systematic Assessment |
| ||
| confusion | Nervous system disorders | Systematic Assessment |
| ||
| depression | Psychiatric disorders | Systematic Assessment |
| ||
| Anxiety | Psychiatric disorders | Systematic Assessment |
| ||
| Anxiety, Insomnia | Psychiatric disorders | Systematic Assessment |
| ||
| Kidney stone pain | Renal and urinary disorders | Systematic Assessment |
| ||
| SOB/Fatigue | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Cough, fever chills, pain with breathing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Shortness of breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Bronchitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Elevated Glucose | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Sinus blockage | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| lung infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| cough, wheeze, congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
Not provided
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Wonder Drake, MD | Vanderbilt University Medical Center | (615) 322-2035 | wonder.drake@vumc.org |
| Jun 16, 2020 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D012507 | Sarcoidosis |
| ID | Term |
|---|---|
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006968 | Hypersensitivity, Delayed |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D064704 | Levofloxacin |
| D004977 | Ethambutol |
| D017963 | Azithromycin |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D015242 | Ofloxacin |
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D005029 | Ethylenediamines |
| D003959 | Diamines |
| D011073 | Polyamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
| Participants |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|