Early Treatment Strategy With High-dose Dexamethasone in Patients With SARS-CoV-2

NCT ID: NCT05293210

Last Updated: 2023-03-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-28
• Study Completion Date: 2023-12-01

Brief Summary

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

Detailed Description

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.

Conditions

Covid19; Dexamethasone

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental arm

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.

Group Type: EXPERIMENTAL

Dexamethasone

Intervention Type: 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).

Standard treatment regimen

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).

Group Type: ACTIVE_COMPARATOR

Dexamethasone

Intervention Type: 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).

Interventions

Dexamethasone

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).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients admitted with SARS-CoV-2 (COVID19) pneumonia confirmed by antigenic test or PCR Age ≥ 18 yrs.
• pcr ≥ 66 mg/L and ≤150 mg/L at inclusion or Pandemic score at admission > 200 with pcr 9.7-149 mg/L at inclusion.
• WHO scale level 4, with need for oxygen therapy in NG ≥ 1 lpm to maintain saturation ≥ 94%.
• Onset of symptoms ≤ 10 days before the date of inclusion.
• After having received verbal and written information about the study, the patient must submit the signed and dated Informed Consent before performing any activity related to the study.

Exclusion Criteria

• Patients with respiratory distress criteria at the time of randomization, understood as need for OCNAF/VMNI/VMI (levels 5 and 6 of the WHO scale) or O2 saturation ≤ 92% and/or FR ≥ 30 despite oxygen in NG at 4 liters.
• Patients with allergy or contraindication to the use of systemic corticosteroids.
• Patients with severe asthma or chronic pulmonary pathology with home oxygen requirements and active treatment with corticosteroids.
• Patients on chronic corticosteroid treatment.
• Use of corticosteroids daily in the 15 days prior to hospital admission.
• Indication of corticosteroid use due to other clinical conditions of the patient (e.g., septic shock).
• Pregnant or actively breastfeeding women
• Patients with suspected or confirmed bacterial, fungal, or viral infection other than SARS-CoV-2 itself at the time of randomization
• Patients with confirmed past or latent tuberculosis infection prior to inclusion.
• Patients with known HIV infection with CD4 below 500 cells/mm3 or on active treatment with protease inhibitors or boosters such as cobicistat or ritonavir.
• Patients with active oncologic processes in the last year or in active treatment with chemotherapy.
• Patients with life expectancy < 3 months at inclusion due to clinical conditions other than SARS-CoV-2 pneumonia.
• Patients with expected death in the following 48-72 hours.
• Patients included in another clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Universitario Infanta Leonor

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maria Carranza, MD

Role: PRINCIPAL_INVESTIGATOR

Infanta Leonor University Hospital

Central Contacts

Maria Carranza, MD

Role: CONTACT

mariadecarranza@gmail.com

+34 911 91 80 00

Angel Pueyo, PHD

Role: CONTACT

angel.pueyo@salud.madrid.org

+34 618448807

Other Identifiers

PREDEXACOV

Identifier Type: -

Identifier Source: org_study_id