Clinical Trials Register

Summary
EudraCT Number:	2020-001766-11
Sponsor's Protocol Code Number:	2020-24
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-04-15
Trial 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

France - ANSM

A.2

EudraCT number

2020-001766-11

A.3

Full title of the trial

Losartan and spironolactone treatment for COVID-19 patients with acute respiratory failure in intensive care unit

Intérêt du traitement par losartan et de la spironolactone sur la régulation du système rénine-angiotensine dans le pronostic des patients infectés par COVID-19 et atteints d’un syndrome de détresse respiratoire aiguë

A.3.1

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

Losartan and spironolactone treatment for COVID-19 patients with acute respiratory failure in intensive care unit

A.3.2

Name or abbreviated title of the trial where available

COVIDANCE

A.4.1

Sponsor's protocol code number

2020-24

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	ASSISTANCE PUBLIQUE HÔPITAUX DE MARSEILLE
B.1.3.4	Country	France
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	ASSISTANCE PUBLIQUE HÔPITAUX DE MARSEILLE
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ASSISTANCE PUBLIQUE HÔPITAUX DE MARSEILLE
B.5.2	Functional name of contact point	clinical project manager
B.5.3	Address:
B.5.3.1	Street Address	DRS, 80 Rue Brochier
B.5.3.2	Town/ city	Marseille
B.5.3.3	Post code	13354 Cedex 05
B.5.3.4	Country	France
B.5.4	Telephone number	0491382183
B.5.5	Fax number	0491381479
B.5.6	E-mail	promotion.interne@ap-hm.fr

D. IMP Identification
D.IMP: 1
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	LOSARTAN ARROW 50 mg, comprimé pelliculé sécable
D.2.1.1.2	Name of the Marketing Authorisation holder	Arrow Génériques
D.2.1.2	Country which granted the Marketing Authorisation	France
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.3.1	Product name	Losartan
D.3.2	Product code	Losartan
D.3.4	Pharmaceutical form	Pillules
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LOSARTAN
D.3.9.1	CAS number	114798-26-4
D.3.9.2	Current sponsor code	losartan
D.3.9.4	EV Substance Code	SUB08593MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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	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	SPIRONOLACTONE ARROW 25 mg, comprimé pelliculé sécable
D.2.1.1.2	Name of the Marketing Authorisation holder	Arrow génériques
D.2.1.2	Country which granted the Marketing Authorisation	France
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.3.1	Product name	SPIRONOLACTONE
D.3.2	Product code	SPIRONOLACTONE
D.3.4	Pharmaceutical form	Pillules
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	SPIRONOLACTONE
D.3.9.2	Current sponsor code	SPIRONOLACTONE
D.3.9.4	EV Substance Code	SUB10631MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
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

Patients with Covid-19

Patients atteints de Covid-19

E.1.1.1

Medical condition in easily understood language

Covid-19 Infection

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 show the interest of treatment with losartan and spironolactone in patients infected with COVID-19 and suffering from acute respiratory distress syndrome on the impact of organ failures judged on the SOFA score on the 7th day post-inclusion

Montrer l’intérêt du traitement par losartan et de spironolactone chez les patients infectés par COVID-19 et atteints d’un syndrome de détresse respiratoire aigüe sur l’impact des défaillances d’organes jugé sur le score SOFA au 7e jour post-inclusion

E.2.2

Secondary objectives of the trial

Show the interest of ARA2 / Spironolactone treatment on organ failures judged on the SOFA score on the 3rd, 14th, 21st, 28th day post-inclusion.
Show the interest of ARA2 / Spironolactone treatment on oxygenation based on the PaO2 / FiO2 ratio.
Show the interest of ARA2 / Spironolactone treatment for the duration of mechanical ventilation.
To show the interest of ARA2 / Spironolactone treatment on mortality.
Evaluate the clinical and biological tolerance of these treatments.

Montrer l’intérêt du traitement par ARA2/Spironolactone sur les défaillances d’organes jugé sur le score SOFA au 3ème, 14ème, 21ème, 28ème jour post-inclusion.
Montrer l’intérêt du traitement par ARA2/Spironolactone sur l’oxygénation basé sur le rapport PaO2/FiO2.
Montrer l’intérêt du traitement par ARA2/Spironolactone sur la durée de ventilation mécanique.
Montrer l’intérêt du traitement par ARA2/Spironolactone sur la mortalité.
Evaluer la tolérance clinique et biologique de ces traitements.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Major patient
Patient with respiratory distress requiring oxygen support greater than or equal to 6 liters per minute.
News-Score greater than 6
PCR SARS-CoV-2 positive in a pharyngeal or respiratory sample,
Informed Consent

Patient majeur
Patient avec détresse respiratoire nécessitant un support d’oxygène supérieur ou égal à 6 litres par minute.
News-Score supérieur à 6
PCR SARS-CoV-2 positive dans un prélèvement pharyngé ou respiratoire,
Recueil du consentement éclairé

E.4

Principal exclusion criteria

Minor patient,
Patient deprived of liberty,
Patient's refusal to participate in the study,
Patient for whom therapeutic limitation measures have been issued justifying the absence of mechanical ventilation,
Patient aged 80 or over,
Hypotension justifying treatment with noradrenaline,
Acute renal failure with a clearance of less than 60ml / min,
Severe liver failure.
Intolerance or contraindication to losartan or spironolactone.

Patient mineur,
Patient privé de liberté,
Refus du patient de participer à l’étude,
Patient pour lequel ont été émises des mesures de limitations thérapeutiques justifiant l’absence de recours à la ventilation mécanique,
Patient de 80ans ou plus,
Hypotension justifiant un traitement par noradrénaline,
Insuffisance rénale aigue avec une clairance inférieure à 60ml/min,
Insuffisance hépatique grave.
Intolérance ou contre-indication au losartan ou au spironolactone.

E.5 End points

E.5.1

Primary end point(s)

Organ failures will be assessed on the SOFA score

Les défaillances d’organes seront évaluées sur le score SOFA

E.5.1.1

Timepoint(s) of evaluation of this end point

7th day post-inclusion

7e jour post-inclusion

E.5.2

Secondary end point(s)

Organ failures will be assessed on the SOFA score
Oxygenation will be assessed using the PaO2 / FiO2 report
The duration of mechanical ventilation will be evaluated by the number of ventilation days, the number of days without ventilation between inclusion and death or D28.
Mortality will be measured by: mortality on D28, hospital mortality, resuscitation mortality.
The clinical tolerance will be evaluated by the permanent measurement of blood pressure, heart rate and diuresis, biological by the assays of urea, creatinine, potassium and markers of liver function.

Les défaillances d’organes seront évaluées sur le score SOFA
L’oxygénation sera évaluée à l’aide du rapport PaO2/FiO2
La durée de la ventilation mécanique sera évaluée par le nombre de jours de ventilation, le nombre de jours sans ventilation entre inclusion et décès ou J28.
La mortalité sera mesurée par : mortalité à J28, mortalité hospitalière, mortalité en réanimation.
La tolérance clinique sera évaluée par la mesure permanente de la tension artérielle, fréquence cardiaque et la diurèse, biologique par les dosages de l’urée, créatinine, kaliémie et des marqueurs de la fonction hépatique.

E.5.2.1

Timepoint(s) of evaluation of this end point

3rd, 14th, 21st, 28th day post-inclusion

3ème, 14ème , 21ème, 28ème jour post-inclusion

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

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

Yes

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

groupe contrôle

group control

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

Yes

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

DVDP

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

E.8.9.2

In all countries concerned by the trial months

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients in intensive care

Patients en réanimation

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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

non

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

2020-04-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-24

P. End of Trial
P.	End of Trial Status	Ongoing

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