Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial

NCT04360876 | Withdrawn Phase 2 DMC

• 1 other identifier: 20-0811
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This trial will determine the safety and estimate efficacy of targeted corticosteroids in mechanically ventilated patients with the hyper-inflammatory sub phenotype of ARDS due to coronavirus disease 2019 (COVID-19) by implementing a Phase 2A clinical trial.

Conditions

COVID-19; ARDS

Keywords

Corticosteroids; Dexamethasone; COVID-19 Pneumonia; ARDS

Outcome Measures

Primary Outcomes (1)

• Ventilator Free Days (VFD) at Day 28

  Total number of ventilator free days to day 28 of hospitalization. If a patient dies prior to day 28, they will be counted as zero ventilator free days. Follow up will be performed via phone or electronically to determine ventilator free status of those patients discharged prior to day 28.

  28 Days

Secondary Outcomes (18)

• Clinical Status at day 14 as measured by World Health Organization (WHO) 7-point ordinal scale.

  14 Days

• Clinical Status at day 28 as measured by WHO 7-point ordinal scale

  28 Days

• In-Hospital Mortality at day 28

  28 Days

• In-Hospital Mortality at day 90

  90 Days

• Time to Mortality to day 28

  28 Days

Study Arms (2)

Dexamethasone

EXPERIMENTAL

Patients assigned to the dexamethasone arm will receive an intravenous dose of 20 mg once daily from day 1 to day 5 which will be reduced to 10mg once daily from day 6 to day 10. Intravenous infusion bags divided into 10 doses will be provided at randomization by the investigational pharmacy. The time from randomization to time for first medication administration will be 4 hours or less. All infusions - dexamethasone and placebo - will be manufactured by the investigational pharmacy at the University of Colorado.

Drug: Dexamethasone injection

Placebo

PLACEBO COMPARATOR

Participants randomized to the control group will received placebo intravenously for 10 days, one dose per day. Intravenous infusion bags divided into 10 doses will be provided at randomization by the investigational pharmacy. The placebo infusion bags will be as similar as possible to the dexamethasone infusion bags to ensure blinding.

Drug: Placebos

Interventions

Dexamethasone injection DRUG

Dexamethasone intravenous 20mg daily for 5 days followed by 10mg daily for 5 days

Dexamethasone

Placebos DRUG

Placebo delivered intravenously on the same dosing schedule as dexamethasone

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female Adult ≥ 18 years of age at time of enrollment
• Laboratory confirmed SARS-CoV-2 infection determined by PCR within 14 days prior to randomization and no alternative explanation for current clinical condition
• Moderate or Severe ARDS (PaO2:FiO2 ratio ≤ 200mmHg) requiring mechanical ventilation within 7 days prior to randomization
• Hyper-inflammatory ARDS Sub-Phenotype defined as any one of the following:
• C-Reactive Protein (CRP) \> 100mg/dL
• D-Dimer \> 600ng/mL
• IL-6 \> 10pg/mL
• Willing and/or able to comply with study-related procedures and assessments
• Provide informed consent signed by study patient or legally acceptable representative

You may not qualify if:

• Age \< 18 years
• In the opinion of the investigator, not expected to survive for more than 48 hours from screening
• Presence of any of the following abnormal laboratory values at screening
• Absolute neutrophil count (ANC) \< 2,000mm3
• Alanine Transferase (ALT) or Aspartate Transferase (AST) \> 5 times upper limit of normal
• Use of systemic corticosteroid therapy within 7 days of study enrollment
• Known or suspected active bacterial, fungal or mycobacterial infections including tuberculosis (TB)
• Participation in a double-blind clinical research study evaluating an investigational product or therapy within 3 months and less than 5 half-lives of investigational product prior to the screening visit. Exception: The use of remdesivir, hydroxychloroquine, or other treatments being used for COVID-19 infection in the context of an open-label study or compassionate use protocol is permitted
• Any physical examination findings, and/or history of any illness, concomitant medication or recent live vaccines that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study
• Prisoner
• Pregnancy

Sponsors & Collaborators

• University of Colorado, Denver: lead

MeSH Terms

Conditions

COVID-19

Interventions

Calcium Dobesilate

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Participants confirmed to meet all eligibility criteria who have provided informed consent will be randomized 1:1 to dexamethasone versus placebo. A randomized group assignment will be provided to the investigator or research assistant. Randomization will be performed according to a central randomization scheme and will stratified by site in permuted blocks of varying size.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-center, Phase 2a, pragmatic, randomized, double-blinded, placebo-controlled

Study Record Dates

• First Submitted: April 22, 2020
• First Posted: April 24, 2020
• Study Start: September 1, 2020
• Primary Completion: December 31, 2020
• Study Completion: January 30, 2021
• Last Updated: October 28, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share