Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19

NCT04663555 | Completed Phase 4 DMC

• 2 other identifiers: CZECRIN No. 2020/472020-005887-70
• Study Type: interventional
• Target: 235
• Locations: 1 country
• Sites: 1

Brief Summary

REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice. The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed.

Conditions

Covid19; ARDS

Keywords

Covid19; ARDS; dexamethasone

Outcome Measures

Primary Outcomes (1)

• Number of ventilator-free days (VFDs) at 28 days after randomization

  Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation (more than 48 hours)

  28 days

Secondary Outcomes (5)

• Mortality from any cause at 60 days after randomization

  60 days

• WHO clinical progression scale at day 14

  14 days

• Dynamics of inflammatory marker

  14 days

• Adverse events related to corticosteroids

  28 days

• Functional independence

  90 days

Other Outcomes (2)

• Long-term outcome regarding mortality

  180 and 360 days

• Long-term outcome regarding functional independence

  180 and 360 days

Study Arms (2)

DEX 20 mg

EXPERIMENTAL

Patients in the intervention group after randomization will receive dexamethasone 20 mg intravenously once daily on day 1-5, followed by dexamethasone 10 mg intravenously once daily on day 6-10.

Drug: Dexamethasone

DEX 6 mg

ACTIVE COMPARATOR

Patients in the control group after randomization will receive dexamethasone 6 mg day 1-10.

Drug: Dexamethasone

Interventions

Dexamethasone DRUG

Patients in the intervention group after randomization will receive dexamethasone 20 mg intravenously once daily on day 1-5, followed by dexamethasone 10 mg intravenously once daily on day 6-10. If successful extubation occurs before day 10, treatment with dexamethasone is withdrawn.

DEX 20 mg; DEX 6 mg

Eligibility Criteria

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

You may qualify if:

• Subjects will be eligible for the trial if they meet all of the following criteria:
• Adult (≥ 18 years of age) at time of enrolment;
• Present COVID-19 (infection confirmed by RT-PCR or antigen testing);
• Intubation/mechanical ventilation or ongoing high-flow nasal cannula (HFNC) oxygen therapy;
• Moderate or severe ARDS according to Berlin criteria:
• Moderate - PaO2/FiO2 100-200 mmHg;
• Severe - PaO2/FiO2 \< 100 mmHg;
• Admission to ICU in the last 24 hours.

You may not qualify if:

• Subjects will not be eligible for the trial if they meet any of the following criteria:
• Known allergy/hypersensitivity to dexamethasone or excipients of the investigational medicinal product (e.g. parabens, benzyl alcohol);
• Fulfilled criteria for ARDS for ≥ 14 days at enrolment;
• Pregnancy or breastfeeding;
• Unwillingness to comply with contraception measurements from the enrolment to at least 1 week after the last dose of dexamethasone (sexual abstinence is considered as the adequate contraception method);
• End-of-life decision or patient is expected to die within next 24 hours;
• Decision not to intubate or ceilings of treatment in place;
• Immunosuppression and/or immunosuppressive drugs in medical history:
• Systemic immunosuppressive drugs or chemotherapy in the past 30 days;
• Systemic corticosteroids use before hospitalization;
• Any dose of dexamethasone during the present hospital stay for COVID-19 for more than (≥) last 5 days before enrolment;
• Systemic corticosteroids during present hospital stay for other conditions than COVID-19 (e.g. septic shock);
• Present haematological or generalized solid malignancy;
• Any of contraindications of corticosteroids, e.g.
• intractable hyperglycaemia;

Sponsors & Collaborators

• Brno University Hospital: lead
• Masaryk University: collaborator
• Vascular surgery, University hospital Královské Vinohrady, Prague: collaborator
• General University Hospital, Prague: collaborator
• University Hospital Ostrava: collaborator
• St. Anne's University Hospital Brno: collaborator
• Motol University Hospital: collaborator
• University Hospital Olomouc: collaborator
• University Hospital Plzeň: collaborator
• Tomáš Baťa Regional Hospital: collaborator
• Military University Hospital Praha: collaborator

Study Sites (1)

University Hospital Brno

Brno, 62500, Czechia

Location

Related Publications (15)

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• Malaska J, Stasek J, Duska F, Balik M, Maca J, Hruda J, Vymazal T, Klementova O, Zatloukal J, Gabrhelik T, Novotny P, Demlova R, Kubatova J, Vinklerova J, Svobodnik A, Kratochvil M, Klucka J, Gal R, Singer M; REMED Study Group. Effect of dexamethasone in patients with ARDS and COVID-19 (REMED trial)-study protocol for a prospective, multi-centre, open-label, parallel-group, randomized controlled trial. Trials. 2022 Jan 15;23(1):35. doi: 10.1186/s13063-021-05963-6.

  PMID: 35033182 DERIVED

• Malaska J, Stasek J, Duska F, Balik M, Maca J, Hruda J, Vymazal T, Klementova O, Zatloukal J, Gabrhelik T, Novotny P, Demlova R, Kubatova J, Vinklerova J, Svobodnik A, Kratochvil M, Klucka J, Gal R, Singer M; REMED Study Group. Effect of dexamethasone in patients with ARDS and COVID-19 - prospective, multi-centre, open-label, parallel-group, randomised controlled trial (REMED trial): A structured summary of a study protocol for a randomised controlled trial. Trials. 2021 Mar 1;22(1):172. doi: 10.1186/s13063-021-05116-9.

  PMID: 33648568 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Dexamethasone

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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD. Ph.D. EDIC

Model Details: REMED is a prospective phase II open-label randomized controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The study is multi-centre and will be conducted in intensive care units (ICUs) of university hospitals in the Czech Republic. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are very close to the real-life routine clinical practice. Dexamethasone will be administered once daily intravenously for 10 days. 300 participants will be enrolled and followed up for 360 days after randomization. Following stratification factors will be applied: * Age \< 65 and ≥ 65 (12); * Charlson Comorbidity index (CCI; APPENDIX B Assessment tools, scores, and scales, Chapter 14.2) \< 3 and ≥ 3; * CRP \< 150 mg/L and ≥ 150 mg/L * Trial centre. Patients will be randomized in 1 : 1 ratio in one of the two treatment arms. Randomization through eCRF will be available 24 hours every day.

Study Record Dates

• First Submitted: December 9, 2020
• First Posted: December 11, 2020
• Study Start: February 2, 2021
• Primary Completion: March 9, 2022
• Study Completion: February 23, 2023
• Last Updated: March 22, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: De-identified participant-level dataset will be made available 6 months after the publication of the results of the study at www.mendeley.com
• Access Criteria: Planned IPD metaanalysis or other relevant request

Locations

CZ (1)