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| Name | Class |
|---|---|
| Constant Therapeutics LLC | INDUSTRY |
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The purpose of this study is to determine if administration of angiotensin-(1-7) (TXA127) prevents acute kidney injury and deterioration into multi-organ failure in patients with severe COVID-19. Participants will undergo a 10-day treatment with either placebo or study drug. The drug will be administered intravenously for 3 hours once each day for 10 days consecutively.
Corona virus disease 2019 (COVID-19) has been associated with severe respiratory and multiorgan failure. Research shows that COVID-19 reduces levels of angiotensin-converting enzyme-2 (ACE-2), an enzyme that converts angiotensin II to angiotensin 1-7 (known as TXA127). COVID-19 reduces levels of ACE-2 and therefore angiotensin 1-7 and as a result, angiotensin II levels are going to be increased. Many clinical observations in COVID-19 have shown the high incidence of acute kidney injury that may be due to excessive levels of angiotensin II. The investigators hypothesize that administration of angiotensin (1-7) replaces levels of ACE-2 in COVID-19 and thereby ameliorates deterioration of multi-organ failure and specifically acute kidney injury.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TXA127 | Experimental | Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days). |
|
| Placebo | Placebo Comparator | Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TXA127 | Drug | 0.5 mg/kg per day |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change of Serum Creatinine | Calculated from baseline (at enrollment) to end of study | Day 1 and Day 10 |
| Number of Participants Requiring Intubation | From Day 1 to Day 10 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Requiring Dialysis | Up to Day 10 | |
| Number of Participants Requiring a Vasopressors | Up to Day 10 | |
| Percent Change in Supplemental Oxygen Requirements |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jeanine D'Armiento, MD, PhD | Associate Professor of Medicine in Anesthesiology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Columbia University Irving Medical Center | New York | New York | 10032 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35902867 | Derived | Wagener G, Goldklang MP, Gerber A, Elisman K, Eiseman KA, Fonseca LD, D'Armiento JM. A randomized, placebo-controlled, double-blinded pilot study of angiotensin 1-7 (TXA-127) for the treatment of severe COVID-19. Crit Care. 2022 Jul 28;26(1):229. doi: 10.1186/s13054-022-04096-9. No abstract available. |
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| ID | Title | Description |
|---|---|---|
| FG000 | TXA127 | Participants received one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days). TXA127: 0.5 mg/kg per day |
| FG001 | Placebo | Participants received one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days). Placebo: 0.5 mg/kg per day |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
We included in our analysis participants whom completed minimum of 1 day of drug/placebo.
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| ID | Title | Description |
|---|---|---|
| BG000 | TXA127 | Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days). TXA127: 0.5 mg/kg per day |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 of Serum Creatinine | Calculated from baseline (at enrollment) to end of study | Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis - which is not the same as those who "completed" the study as seen under Participant Flow. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group. | Posted | Mean | Full Range | mg/dL | Day 1 and Day 10 |
|
Adverse event data was collected from Day 1 to Day 10 of study drug/placebo administration (or as long as hospitalized if less than 10 days) and at Day 28 and Day 60 (post hospital discharge) during a follow-up phone call.
Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis - which is not the same as those who "completed" the study as seen under Participant Flow. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.
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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 | TXA127 | Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days). TXA127: 0.5 mg/kg per day |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Intubation | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Right abdominal side pain | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jeanine D'Armiento / Principal Investigator | Columbia University Irving Medical Center | 212-305-3745 | jmd12@cumc.columbia.edu |
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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 | Aug 25, 2021 | Apr 27, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D009102 | Multiple Organ Failure |
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C118790 | angiotensin I (1-7) |
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Double-blinded, placebo-control, randomized clinical trial
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| Placebo | Drug | 0.5 mg/kg per day |
|
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| Day 1 and Day 10 |
| Days of Hospital Stay and Drug Administration | Day 1 to Day 10 |
| Cytokine Levels on the Day of Drug/TXA Administration | Day 1 |
| Cytokine Levels on the Day 5 of Drug/TXA Administration | Day 5 |
| Mortality | Day 1 to Day 10 |
Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).
Placebo: 0.5 mg/kg per day
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
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| Oxygen at randomization | Count of Participants | Participants |
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Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).
Placebo: 0.5 mg/kg per day
|
|
| Primary | Number of Participants Requiring Intubation | Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group. | Posted | Count of Participants | Participants | From Day 1 to Day 10 |
|
|
|
| Secondary | Number of Participants Requiring Dialysis | Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group. | Posted | Count of Participants | Participants | Up to Day 10 |
|
|
|
| Secondary | Number of Participants Requiring a Vasopressors | Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group. | Posted | Count of Participants | Participants | Up to Day 10 |
|
|
|
| Secondary | Percent Change in Supplemental Oxygen Requirements | Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group. | Posted | Mean | Full Range | percent change of oxygen | Day 1 and Day 10 |
|
|
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| Secondary | Days of Hospital Stay and Drug Administration | Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group. | Posted | Median | Inter-Quartile Range | days | Day 1 to Day 10 |
|
|
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| Secondary | Cytokine Levels on the Day of Drug/TXA Administration | Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group. | Posted | Median | Inter-Quartile Range | pg/ml | Day 1 |
|
|
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| Secondary | Cytokine Levels on the Day 5 of Drug/TXA Administration | Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group. | Posted | Median | Inter-Quartile Range | pg/ml | Day 5 |
|
|
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| Secondary | Mortality | Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group. | Posted | Count of Participants | Participants | Day 1 to Day 10 |
|
|
|
| 2 |
| 11 |
| 3 |
| 11 |
| 7 |
| 11 |
| EG001 | Placebo | Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days). Placebo: 0.5 mg/kg per day | 1 | 9 | 2 | 9 | 5 | 9 |
| Diaphoresis | General disorders | Non-systematic Assessment |
|
| Refractory Hypoxemia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Refractory Hypotension | Vascular disorders | Non-systematic Assessment |
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| Headache | General disorders | Non-systematic Assessment |
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| Vertigo | General disorders | Non-systematic Assessment |
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| Hematochezia | Gastrointestinal disorders | Non-systematic Assessment | Blood in stool |
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| Nausea | General disorders | Non-systematic Assessment |
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| Fatigue | General disorders | Non-systematic Assessment |
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| Tachycardia | Cardiac disorders | Non-systematic Assessment |
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| Dyshidrotic Dermatitis | Skin and subcutaneous tissue disorders | Non-systematic Assessment | Itchy hands and feet |
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| Fever | General disorders | Non-systematic Assessment |
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| Tussis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Angina Pectoris | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Chest Tightness |
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| Cloudiness of Consciousness | General disorders | Non-systematic Assessment | Brain fog |
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| Myalgia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Transient Paresthesia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment | Numbness in left leg |
|
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| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012769 | Shock |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| IL-1Ra |
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| IL-10 |
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| IL-12p40 |
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| IL-12p70 |
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| IL-13 |
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| IL-2 |
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| TNF-α |
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| IL-12p40 |
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| IL-12p70 |
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| IL-13 |
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| MCP-1 |
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