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Early identification and treatment of this inflammatory cascade using existing therapeutic strategies with proven safety profiles could change the course and prognosis of COVID-19 infection, reducing mortality rates. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death
The use of corticosteroids in COVID 19 in hospitalized patients with moderate symptoms has not been adequately studied in randomized clinical trials, the studies and clinical trials having focused on critical or severe patients. The few studies available to date have yielded evidence of low certainty.
Our trial postulates that early intervention and treatment with high-dose corticosteroids (20 mg dexamethasone for 3 days) in patients admitted with pneumonia with respiratory failure and moderate elevation of acute phase reactants and proinflammatory cytokines, or with risk factors that condition worse prognosis on admission, and who have not yet developed data on respiratory distress, the development of the cytokine storm could be avoided or minimized, reducing lung tissue damage and progression to severe respiratory failure and, therefore, reducing the need for invasive and noninvasive respiratory therapies, reducing hospital stay and, possibly, reducing associated mortality.
Dexamethasone is a potent synthetic glucocorticoid with actions resembling those of steroid hormones. It acts as an anti-inflammatory and immunosuppressant. It is a widely known glucocorticoid, studied and used in the treatment of autoimmune diseases, in oncology patients under chemotherapy to counteract certain side effects of their antitumor treatment, to augment the antiemetic effects of 5-HT3 receptor antagonists, in patients with brain neoplasms (primary or metastatic) to reduce edema, in spinal cord compressions, in certain hematological malignancies, in the treatment of arthropathies, to counteract allergic shock and septic shock, among many other indications for use. It is also used for the diagnosis of diseases related to hypothalamic-pituitary-adrenal axis dysfunction.
Recently, following the DEXA-COVID, CoDEX and RECOVERY clinical trials, dexamethasone has been widely used in patients with severe or critical SARS-CoV-2 pneumonia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental arm | Experimental | A daily dose of dexamethasone 20 mg intravenous for 3 days, followed by a daily dose of dexamethasone 6 mg intravenous or oral for 7 days. |
|
| Standard treatment regimen | Active Comparator | Dexamethasone 6 mg orally or intravenously for 10 days (with the possibility of escalation to doses of 20 mg daily of oral or intravenous dexamethasone for 3 days if clinical criteria of respiratory distress develop despite treatment with doses of dexamethasone 6 mg daily). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexamethasone | Drug | A daily dose of dexamethasone 20 mg intravenous for 3 days, followed by a daily dose of dexamethasone 6 mg intravenous or oral for 7 days. Dexamethasone 6 mg orally or intravenously for 10 days (with the possibility of escalation to doses of 20 mg daily of oral or intravenous dexamethasone for 3 days if clinical criteria of respiratory distress develop despite treatment with doses of dexamethasone 6 mg daily). |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate if there is a decrease in the proportion of patients who develop respiratory distress |
| Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate if there is a decrease in the number of therapy days |
| W12 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Maria Carranza, MD | Contact | +34 911 91 80 00 | mariadecarranza@gmail.com | |
| Angel Pueyo, PHD | Contact | +34 618448807 | angel.pueyo@salud.madrid.org |
| Name | Affiliation | Role |
|---|---|---|
| Maria Carranza, MD | Infanta Leonor University Hospital | Principal Investigator |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D003907 | Dexamethasone |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
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The study consists of 2 phases:
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Patients who meet all inclusion criteria and none of the exclusion criteria will be randomized to receive a daily dose of dexamethasone 20 mg intravenous for 3 days, followed by a daily dose of oral or intravenous dexamethasone 6 mg for 7 more days versus the center's standard treatment which includes the use of oral or intravenous dexamethasone 6 mg for 10 days with escalation to a daily dose of oral or intravenous dexamethasone 20 mg for 3 days if clinical criteria of respiratory distress develop despite treatment with dexamethasone 6 mg daily.
Randomization will be performed in a centralized manner. Randomization will be done directly in the database itself by including the patient in the CRD-e (Redcap). When the investigator registers a patient in the CRD-e, the system will directly assign him/her to which group he/she has been randomized.
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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 |
| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |