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

Sponsor

Hospital Universitario Infanta Leonor (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05293210

Collaborator

(none)

200

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Covid19 Dexamethasone	Drug: Dexamethasone	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

None (Open Label)

Masking Description:

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.

Primary Purpose:

Treatment

Official Title:

Early Treatment Strategy With High-dose Dexamethasone Versus Standard Dose in Patients With SARS-CoV-2 Pneumonia (COVID-19). PREDEXACOV Study

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: 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).
Active Comparator: 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).	Drug: 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).

Arm

Intervention/Treatment

Experimental: 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.

Drug: 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).

Active Comparator: 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).

Drug: Dexamethasone

Outcome Measures

Primary Outcome Measures

Evaluate if there is a decrease in the proportion of patients who develop respiratory distress [Week 12]
To evaluate whether there is a decrease in the proportion of patients who develop respiratory distress with the need for NIV/MIV/OCNAF (measured group and individually by respiratory therapies). To evaluate the impact of this strategy on the number of days of hospitalization.

Secondary Outcome Measures

Evaluate if there is a decrease in the number of therapy days [W12]
To evaluate whether there is a decrease in the number of NIV/MIV/OCNAF therapy days. To evaluate whether there is a decrease in all-cause mortality at 30, 60 and 90 days. Safety: short- and long-term adverse events related to the following

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Hospital Universitario Infanta Leonor

Investigators

Principal Investigator: Maria Carranza, MD, Infanta Leonor University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hospital Universitario Infanta Leonor

ClinicalTrials.gov Identifier:

NCT05293210

Other Study ID Numbers:

PREDEXACOV

First Posted:

Mar 24, 2022

Last Update Posted:

Aug 4, 2022

Last Verified:

Apr 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Hospital Universitario Infanta Leonor

dexamethasone

covid19

Additional relevant MeSH terms:

COVID-19

Dexamethasone

Study Results

No Results Posted as of Aug 4, 2022