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The trial prematurely terminated due to the loss of funding.
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Despite an organized treatment approach outlined in expert-consensus guidelines for sepsis with fluid resuscitation to treat hypovolemia, antibiotics to target the infectious insult, and vasopressors for hypotension, mortality rates for sepsis remain high and the incidence continues to rise, making sepsis the most expensive inpatient disease.
4,5 Intravenous ascorbic acid therapy decreases organ failure by providing a protective effect on several microvascular functions including improving capillary blood flow, decreasing microvascular permeability, and improving arteriolar responsiveness to vasoconstrictors. Defining the utility of novel agents to augment researchers care for severe sepsis is an important task as investigators continue the institutional focus on sepsis care.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High dose IV ascorbic acid | Active Comparator | Patients will receive 67 mg/kg IV ascorbic acid in 100 ml normal saline over 30 minutes every 8 hours (200 mg/kg/day) for 72 hours. |
|
| Placebo | Placebo Comparator | The placebo group will receive 100 ml 0.9% NaCl over 30 minutes every 8 hours for 72 hours. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ascorbic Acid | Drug |
| ||
| Normal Saline |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Modified SOFA Score | Sequential Organ Failure Assessment (SOFA) Score included the degree of dysfunction of six organ systems (Respiratory, Cardiovascular, Liver, Renal, Coagulation, Neurologic. A modification of the SOFA includes the exclusion of the Liver function. Total score is reported, minimum score = 0 maximum score = 20. Higher scores indicate greater degree of dysfunction. | Baseline and 72 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Modified SOFA Score | Sequential Organ Failure Assessment (SOFA) Score included the degree of dysfunction of six organ systems (Respiratory, Cardiovascular, Liver, Renal, Coagulation, Neurologic. A modification of the SOFA includes the exclusion of the Liver function. Total score is reported, minimum score = 0 maximum score = 20. Higher scores indicate greater dysfunction. | at 72 Hours |
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Inclusion Criteria:
Patients with:
Definition of organ dysfunction:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ryan Arnold, MD | Christiana Care Health Services | Principal Investigator |
| Jamie Rosini, PharmD | Christiana Care Health Services | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chrisitana Care Health System-Christiana Hospital | Newark | Delaware | 19718 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | High Dose IV Ascorbic Acid | Patients will receive 67 mg/kg IV ascorbic acid in 100 ml normal saline over 30 minutes every 8 hours (200 mg/kg/day) for 72 hours. Ascorbic Acid Participant Started: 12 Participant Completed: 9 |
| FG001 | Placebo | The placebo group will receive 100 ml 0.9% NaCl over 30 minutes every 8 hours for 72 hours. Normal Saline Participant Started: 12 Participant Completed: 11 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | High Dose IV Ascorbic Acid | Patients will receive 67 mg/kg IV ascorbic acid in 100 ml normal saline over 30 minutes every 8 hours (200 mg/kg/day) for 72 hours. Ascorbic Acid |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of 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 | Change in Modified SOFA Score | Sequential Organ Failure Assessment (SOFA) Score included the degree of dysfunction of six organ systems (Respiratory, Cardiovascular, Liver, Renal, Coagulation, Neurologic. A modification of the SOFA includes the exclusion of the Liver function. Total score is reported, minimum score = 0 maximum score = 20. Higher scores indicate greater degree of dysfunction. | Data was not available for 3 participants in the treatment group. | Posted | Mean | Standard Deviation | units on a scale | Baseline and 72 hours |
|
2 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 | High Dose IV Ascorbic Acid | Patients will receive 67 mg/kg IV ascorbic acid in 100 ml normal saline over 30 minutes every 8 hours (200 mg/kg/day) for 72 hours. Ascorbic Acid |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | General disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension (SBP< 90) | Vascular disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jamie Rosini, Pharm D | Christiana Care Health Services | 302-733-6364 | jrosini@christianacare.org |
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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 | Jan 11, 2017 | Nov 15, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D018805 | Sepsis |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D001205 | Ascorbic Acid |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D013400 | Sugar Acids |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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|
| Ascorbic Acid Concentration at 32 Hours | Ascorbic Acid Concentration Normal Ascorbic Acid Range 0.4-2.0 mg/dL | 32 Hours |
| ICU Length of Stay | ICU Length of Stay in Hours | Length of ICU stay up to 200 hours |
| Hospital Length of Stay | From admission until discharge from ICU in days | From ICU admission through ICU discharge, up to 2 weeks |
| Change in PIRO Score | PIRO consists of 4 assessments, Predisposition (scored 0-9), Infection (scored 0-4), Response (scored 0-6), and Organ Failure (scored 0-14) (PIRO). The total PIRO score is the sum of all subscores and ranges from 0-33 with higher scores indicating worse health. | Baseline and 72 hours |
| Percentage of Participants Who Died | From initial hospital admission through discharge, up to 2 weeks. |
The placebo group will receive 100 ml 0.9% NaCl over 30 minutes every 8 hours for 72 hours.
Normal Saline
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Ascorbic Acid Concentration, Baseline | Normal Ascorbic Acid Range 0.4-2.0 mg/dL | Missing Data | Mean | Standard Deviation | mg/dL |
|
| Ascorbic Acid Concentrations <0.4 mg/dL, Baseline | Normal Ascorbic Acid Range 0.4-2.0 mg/dL | Missing data | Number | percentage of participants |
|
| PIRO Score, Baseline | PIRO consists of 4 assessments, Predisposition (scored 0-9), Infection (scored 0-4), Response (scored 0-6), and Organ Failure (scored 0-14). The total PIRO score is the sum of all subscores and ranges from 0-33 with higher scores indicating worse health | Mean | Standard Deviation | scores on a scale |
|
| Modified SOFA Score, Baseline | Sequential Organ Failure Assessment (SOFA) Score included the degree of dysfunction of six organ systems (Respiratory, Cardiovascular, Liver, Renal, Coagulation, Neurologic. A modification of the SOFA includes the exclusion of the Liver function. Total score is reported, minimum score = 0 maximum score = 20. Higher scores indicate greater degree of dysfunction. | Mean | Standard Deviation | units on a scale |
|
| ICU Admission | Count of Participants | Participants |
|
The placebo group will receive 100 ml 0.9% NaCl over 30 minutes every 8 hours for 72 hours. Normal Saline |
|
|
|
| Secondary | Modified SOFA Score | Sequential Organ Failure Assessment (SOFA) Score included the degree of dysfunction of six organ systems (Respiratory, Cardiovascular, Liver, Renal, Coagulation, Neurologic. A modification of the SOFA includes the exclusion of the Liver function. Total score is reported, minimum score = 0 maximum score = 20. Higher scores indicate greater dysfunction. | Data was not available for 3 participants in the treatment group. | Posted | Mean | Standard Deviation | units on a scale | at 72 Hours |
|
|
|
|
| Secondary | Ascorbic Acid Concentration at 32 Hours | Ascorbic Acid Concentration Normal Ascorbic Acid Range 0.4-2.0 mg/dL | Posted | Mean | Standard Deviation | mg/dL | 32 Hours |
|
|
|
|
| Secondary | ICU Length of Stay | ICU Length of Stay in Hours | Data was not available for 7 participants in both groups. | Posted | Median | Inter-Quartile Range | Hours | Length of ICU stay up to 200 hours |
|
|
|
|
| Secondary | Hospital Length of Stay | From admission until discharge from ICU in days | Posted | Median | Inter-Quartile Range | Days | From ICU admission through ICU discharge, up to 2 weeks |
|
|
|
|
| Secondary | Change in PIRO Score | PIRO consists of 4 assessments, Predisposition (scored 0-9), Infection (scored 0-4), Response (scored 0-6), and Organ Failure (scored 0-14) (PIRO). The total PIRO score is the sum of all subscores and ranges from 0-33 with higher scores indicating worse health. | Data was not available for 3 participants in the treatment group. | Posted | Mean | Standard Deviation | units on a scale | Baseline and 72 hours |
|
|
|
|
| Secondary | Percentage of Participants Who Died | Posted | Number | Percentage of participants | From initial hospital admission through discharge, up to 2 weeks. |
|
|
|
|
| 2 |
| 12 |
| 2 |
| 12 |
| 6 |
| 12 |
| EG001 | Placebo | The placebo group will receive 100 ml 0.9% NaCl over 30 minutes every 8 hours for 72 hours. Normal Saline | 2 | 12 | 2 | 12 | 4 | 12 |
| Shortness of Breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Short of breath during the 48-72 hour post randomization. |
|
| Tachycardia (HR increase 20 bpm) | Cardiac disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Other | General disorders | Systematic Assessment |
|
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| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D006880 |
| Hydroxy Acids |
| D002241 | Carbohydrates |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |