Clinical trial NCT05293210: Early Treatment Strategy With High-dose Dexamethasone in Patients With SARS-CoV-2
Official title: Early Treatment Strategy With High-dose Dexamethasone Versus Standard Dose in Patients With SARS-CoV-2 Pneumonia (COVID-19). PREDEXACOV Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Covid19
Dexamethasone
Keywords: dexamethasone
covid19
Lead sponsor: Hospital Universitario Infanta Leonor
Sponsor class: OTHER
First posted: 2022-03-24
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study consists of 2 phases:

* Hospitalization phase: Day 1 of IC signature to day of hospital discharge. In case of not having completed 10 days of hospitalization since inclusion, patients will have to complete the 10 days of treatment on an outpatient basis. This medication will be provided by the Hospital Pharmacy. In case of discharge, the information will be obtained from the patients in person or by telephone contact, according to their needs, with the patient himself or his caregivers and/or cohabitants.
* Follow-up phase: outpatient visits at 30, 60 and 90 days. The information is obtained from the patients, from the medical records or by telephone contact with the patient himself or his caregivers and/or cohabitants according to availability and need of the patient.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Evaluate if there is a decrease in the proportion of patients who develop respiratory distress
timeFrame: Week 12
Secondary outcomes:
measure: Evaluate if there is a decrease in the number of therapy days
timeFrame: W12
Other outcomes:
Locations:
Study officials:
affiliation: Infanta Leonor University Hospital
name: Maria Carranza, MD
role: PRINCIPAL_INVESTIGATOR
References: