Clinical Trials Register

Summary
EudraCT Number:	2020-005026-28
Sponsor's Protocol Code Number:	GLUCOCOVID-bolus
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-11-25
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2020-005026-28

A.3

Full title of the trial

USE OF GLUCOCORTICOIDS IN PATIENTS WITH SARS-COV-2 CORONAVIRUS INFECTION. Pragmatic trial inserted in real practice during a pandemic.

USO DE GLUCOCORTICOIDES EN PACIENTES CON INFECCION POR CORONAVIRUS SARS-COV-2. Ensayo pragmático insertado en práctica real durante pandemia.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Treatment with glucocorticoids in COVID patients.

Tratamiento con glucocorticoides en pacientes con COVID

A.3.2

Name or abbreviated title of the trial where available

GLUCOCOVID-bolus

A.4.1

Sponsor's protocol code number

GLUCOCOVID-bolus

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Instituto de Investigación Biomédica de Salamanca (IBSAL) - IECSCYL
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	IBSAL
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IBSAL
B.5.2	Functional name of contact point	Clinical Trial Area
B.5.3	Address:
B.5.3.1	Street Address	Paseo de San Vicente, 52-185
B.5.3.2	Town/ city	Salamanca
B.5.3.3	Post code	37007
B.5.3.4	Country	Spain
B.5.4	Telephone number	349232911005779
B.5.6	E-mail	esperanza.lopez@scren.es

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Fortecortin
D.2.1.1.2	Name of the Marketing Authorisation holder	Laboratorios ERN, S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.1	CAS number	312-93-6
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	DEXAMETHASONE PHOSPHATE
D.3.9.4	EV Substance Code	SUB01612MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	4 to 8
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Fortecortin
D.2.1.1.2	Name of the Marketing Authorisation holder	Laboratorios ERN, S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DEXAMETHASONE
D.3.9.1	CAS number	N/A
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	N/A
D.3.9.4	EV Substance Code	SUB07017MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1 to 8
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Urbason
D.2.1.1.2	Name of the Marketing Authorisation holder	sanofi-aventis, S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Powder for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.1	CAS number	2375-03-3
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	METHYLPREDNISOLONE SODIUM HEMISUCCINATE
D.3.9.4	EV Substance Code	SUB26423
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	8 to 250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Coronavisus disease (COVID-19)

Enfermedad causada por Corovirus-19

E.1.1.1

Medical condition in easily understood language

COVID

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the effect of high-dose methylprednisolone bolus administration against the intermediate-dose dexamethasone pattern (RECOVERY trial) in COVID-19 patients with non-critical respiratory failure.

Comparar el efecto de la administración de bolos de metilprednisolona a dosis alta frente a la pauta de dosis intermedia de dexametasona (ensayo RECOVERY) en pacientes con la COVID-19 con insuficiencia respiratoria no críticos.

E.2.2

Secondary objectives of the trial

- To assess the efficacy profile of the use of high doses of glucocorticoids during a short cycle on mortality in patients with VIDOC-19
- To assess the efficacy profile of the use of high doses of glucocorticoids during a short cycle on the evolution to needing respiratory support (invasive or non-invasive mechanical ventilation) in patients with VOC-19
- To assess the efficacy profile of the use of high doses of glucocorticoids during a short cycle over the time of admission in patients with VIDOC-19
- To assess the safety profile of the administration of high doses of glucocorticoids in relation to the presence of added infections, hyperglycaemias, psychotic conditions or other adverse events.

- Valorar el perfil de eficacia del uso de dosis altas de glucocorticoides durante un ciclo corto sobre la mortalidad en pacientes con COVID-19
- Valorar el perfil de eficacia del uso de dosis altas de glucocorticoides durante un ciclo corto sobre la evolución a necesitar soporte respiratorio (Ventilación mecánica invasiva o no) en pacientes con COVID-19
- Valorar el perfil de eficacia del uso de dosis altas de glucocorticoides durante un ciclo corto sobre el tiempo de ingreso en pacientes con COVID-19
- Valorar el perfil de seguridad de la administración de dosis altas de glucocorticoides en relación a la presencia de infecciones añadidas, hiperglicemias, cuadros sicóticos u otros eventos adversos.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Over 18 years of age
2) Inpatient
3) Diagnosis of SARS-CoV-2 infection confirmed by RT-PCR or antigen
4) They present evidence in computed axial tomography (CT) of pulmonary involvement attributed to the infection by COVID. Patients in whom CT scans are not performed must have suspected pulmonary involvement by clinical examination with simple compatible or suggestive radiology.
5) Requires supplementary oxygen due to basal saturation ≤ 93% (with ambient O2, 21%)

1) Mayores de 18 años
2) Paciente hospitalizado
3) Diagnóstico de infección por SARS-CoV-2 confirmado por RT-PCR o antígeno.
4) Presentan evidencia en tomografía axial computarizada (TC) de afectación pulmonar atribuida a la infección por COVID. Los pacientes en los que no se realice TC deben tener sospecha de afectación pulmonar por clínica con radiología simple compatible o sugerente.
5) Requiere oxígeno suplementario por saturación basal ≤ 93% (con O2 ambiente, 21%)

E.4

Principal exclusion criteria

1) The patient's situation is so serious that the doctor in charge thinks he could die within 24 hours.
2) At the time of randomisation, patients require one of the following 4 ventilatory supports:
a) high-flow oxygen devices.
b) non-invasive mechanical ventilation.
c) invasive mechanical ventilation.
d) Extracorporeal membrane oxygenation (ECMO).
3) The patient is or has been treated in the 2 weeks prior to randomisation with glucocorticoids or inflammation modifying drugs, both conventional (thiopurines, cyclophosphamide, cyclosporine, tracolimus), leflunomide, methotrexate, mycophenolate mofetil/mycophenolic acid, sulfasalazine, hydroxychloroquine or chloroquine) as synthetics or biologics directed against therapeutic targets (abatacept, belimumab, CD-20, IL1, IL6, Il12. 23, IL-23, Il.17, TNF, integrin α4β7 or Janus kinase inhibitors JAK). Patients who are only on maintenance treatment with doses of steroids less than or equal to 7.5 mg of prednisone or equivalent per day will not be excluded.
4) The patient is pregnant or breastfeeding.
5) The patient has a chronic renal disease is stage 4 or 5 (CCr <30 ml/min).
6) Moderate to severe dementia at the investigator's discretion.
7) Hypersensitivity to any of the active ingredients or to any of the excipients included in its formulation.
8) Untreated systemic infections not caused by COVID-19.
9) Active stomach or duodenal ulcer.
10) Recent vaccination with live vaccines.
11) Other infection or disease that explains the lung disorder.
12) Inability of the patient to understand the study or to sign the informed consent unless consent is delegated to a legal representative.
13) Active participation in another clinical study in the last 15 days.

1) La situación del paciente es de tal gravedad que el médico responsable piensa que podría fallecer en las siguientes 24h.
2) Los pacientes precisan en el momento de la aleatorización alguno de los 4 siguientes soportes ventilatorios:
a) dispositivos de alto flujo de oxígeno.
b) ventilación mecánica no invasiva.
c) ventilación mecánica invasiva.
d) oxigenación por membrana extracorpórea (ECMO).
3) El paciente está o ha estado en tratamiento en las 2 semanas previas a la aleatorización con glucocorticoides o fármacos modificadores de la inflamación, tanto convencionales (tiopurinas, ciclofosfamida, ciclosporina, tracolimus, leflunomida, metotrexate, micofenolato mofetil/ácido micofenólico, sulfasalazina, hidroxicloroquina o cloroquina) como sintéticos o biológicos dirigidos contra dianas terapéuticas (abatacept, belimumab, CD-20, IL1, IL6, Il12.23, IL-23, Il.17, TNF, integrina α4β7 o inhibidores de la cinasa Janus JAK). No serán excluidos los pacientes que únicamente estén en tratamiento de mantenimiento con dosis de corticoides inferiores o iguales a 7,5 mg de prednisona o equivalente al día.
4) La paciente está embarazada o en lactancia.
5) El paciente tiene una enfermedad renal crónica es estadio 4 o 5 (CCr <30 ml/min).
6) Demencia moderada a grave a criterio del investigador.
7) Hipersensibilidad a alguno de los principios activos o a alguno de los excipientes incluidos en su formulación.
8) Infecciones sistémicas no tratadas no causadas por COVID-19.
9) Úlcera de estómago o úlcera duodenal activas.
10) La vacunación reciente con vacunas vivas.
11) Existe otra infección o enfermedad que explica el trastorno pulmonar
12) Incapacidad del paciente de comprender el estudio o firmar el consentimiento informado salvo en el caso que se realice un consentimiento delegado en un representante legal.
13) Participación activa en otro estudio clínico en los últimos 15 días.

E.5 End points

E.5.1

Primary end point(s)

Death

Fallecimiento

E.5.1.1

Timepoint(s) of evaluation of this end point

28 days

28 días

E.5.2

Secondary end point(s)

- Admission to Intensive Care Unit after 28 days
- Need for non-invasive mechanical ventilation or high-flow oxygen at 28 days
- Need for mechanical ventilation and intubation at 28 days
- Use of other immunosuppressive drugs.
- Time to discharge (days of hospitalisation from the start of treatment)
- Baseline situation at 3 months after treatment according to the WHO 8-category scale.

- Ingreso en Unidad de Cuidados intensivos a los 28 días
- Necesidad de ventilación mecánica no invasiva u oxígeno a alto flujo a los 28 días.
- Necesidad de ventilación mecánica e intubación a los 28 días.
- Uso de otros fármacos inmunosupresores.
- Tiempo hasta el alta (días de hospitalización desde el inicio del tratamiento)
- Situación basal a los 3 meses del tratamiento según la escala de 8 categorías de la OMS.

E.5.2.1

Timepoint(s) of evaluation of this end point

28 days .
Discharge date.
3 months after treatment.

28 días.
Fecha de alta.
3 meses después del tratamiento.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

Última visita del último paciente

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

190

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

290

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

Ninguno

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-01-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-01-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-11-09

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