Clinical Trials Register

Summary
EudraCT Number:	2020-002287-31
Sponsor's Protocol Code Number:	PREVICHARM
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-05-25
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

Spain - AEMPS

A.2

EudraCT number

2020-002287-31

A.3

Full title of the trial

Prevention of COVID19 infection with hydroxychloroquine in institutionalized older people and nursing home staff. An open, randomized controlled stepped-wedge clinical trial by clusters.
PREVICHARM Study

Prevención de infección por COVID19 mediante administración de hidroxicloroquina en mayores institucionalizados y personal asistencial de residencias. Ensayo clínico controlado, abierto y aleatorizado escalonado (stepped-wedge) por clusters. Estudio PREVICHARM

A.3.1

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

COVID 19 prevention in nursing homes

Prevención COVID 19 en residencias de mayores

A.3.2

Name or abbreviated title of the trial where available

PREVICHARM

A.4.1

Sponsor's protocol code number

PREVICHARM

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	FIMABIS
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	ISCIII
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	FIMABIS
B.5.2	Functional name of contact point	Gloria Luque
B.5.3	Address:
B.5.3.1	Street Address	Estudios Clínicos. 7 planta, pabellón A. Hospital Regional Universitario. Avda Carlos Haya s/n
B.5.3.2	Town/ city	Málaga
B.5.3.3	Post code	29010
B.5.3.4	Country	Spain
B.5.4	Telephone number	34951291977
B.5.5	Fax number	34671951440263
B.5.6	E-mail	gloria.luque@ibima.eu

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	DOLQUINE
D.2.1.1.2	Name of the Marketing Authorisation holder	LABORATORIOS RUBIO
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.3.1	Product name	Hydroxychloroquine
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	Hydroxychloroquine
D.3.9.1	CAS number	118-42-3
D.3.9.4	EV Substance Code	SUB08077MIG
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	400
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

COVID-19

E.1.1.1

Medical condition in easily understood language

COVID-19

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.0
E.1.2	Level	PT
E.1.2	Classification code	10084268
E.1.2	Term	COVID-19
E.1.2	System Organ Class	10021881 - Infections and infestations

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 evaluate the effectiveness of prophylactic administration of hydroxychloroquine in the staff who provide direct care and in institutionalized people, on the incidence of secondary cases of SARS-CoV-2 infection in residents and professionals in the 4 weeks after the start of the trial. The effects on reduction in mortality and hospital admissions, incidence of symptoms, and drug safety will also be evaluated. Likewise, it will be evaluated whether the weekly review of some aspects of infection prevention (staff knowledge of protective measures, cross infection circuits, etc) interacts with hydroxychloroquine chemoprophylaxis.

a) Evaluar la efectividad de la administración de HCQ de forma profiláctica, en personal que proporciona cuidados directos y en residentes, sobre la incidencia de casos secundarios de infección por SARS-CoV-2 en residentes en las 4 semanas posteriores al inicio de la administración de la quimioprofilaxis.
b) Evaluar el impacto en la incidencia de nuevos casos de infección por SARS-CoV-2 en el propio personal que presta cuidados directos en las 4 semanas posteriores al inicio de la administración de la quimioprofilaxis.
c) Evaluar la posible sinergia del tratamiento con la realización de medidas no farmacológicas de promoción de control de la infección en la residencia.

E.2.2

Secondary objectives of the trial

a) Determine the possible impact on the mortality of residents at 14 and 28 days.
b) Know the compliance of the treatment in the professionals included in the treatment.
c) Examine the incidence of typical symptoms of SARS-CoV-2 infection: fever, cough, headache, arthromyalgia, pharyngeal pain, dyspnea, diarrhea, vomiting, abdominal pain, anosmia.
d) Compare the incidence of hospital admissions of staff and residents who contract SARS-CoV-2 infection during the study.
e) Evaluate the safety of the administered chemoprophylactic regimen.
f) Study the proportion of subjects who drop out of the study for any reason.
g) Analyze the proportion of subjects who do not adhere to chemoprophylaxis.

a) Determinar el posible impacto sobre la mortalidad de residentes a los 14 y 28 días.
b) Conocer el cumplimiento del tratamiento en los profesionales incluidos en el tratamiento.
c) Examinar la incidencia de síntomas típicos de infección por SARS-CoV-2: fiebre, tos, cefalea, artro-mialgias, dolor faríngeo, disnea, diarrea, vómitos, dolor abdominal, anosmia.
d) Comparar la incidencia de ingresos hospitalarios del personal y residentes que contraen infección por SARS-CoV-2 durante el estudio.
e) Evaluar la seguridad de la pauta quimioprofiláctica administrada.
f) Estudiar la proporción de sujetos que abandonan el estudio por cualquier razón.
g) Analizar la proporción de sujetos que no se adhieren a la quimioprofilaxis.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

For residents:
1. Institutionalized people in residences since the beginning of the COVID19 epidemic who do not have the infection present at the time of entering the study. In this regard, prior to the first day of evaluation of each residence, a census will be made of residents and professionals who have already had COVID19 verified by RT-PCR. If the last resident or professional has had the disease for more than 15 days, the residence will be excluded from the study. Once the residence was included (because the presence of residents and / or workers exposed to COVID19 has been confirmed less than 15 days ago), the decision to enter the study of each participating subject will be made only by confirmation by baseline RT-PCR, in accordance with the SEIMC recommendations on the use of antibody detection tests in nursing homes21. In addition, until the PCR is available, the decision to enter the study will be delayed.
2. That they give their consent to participate in the study or that it be obtained from their legal representative / guardian (see section on informed consent).

For professionals:
3. Healthcare professionals who do not have the infection present at the time of entering the study, who provide direct care (AUXILIARY and nurses) to institutionalized elderly with confirmed infection of COVID19 in the last 15 days by means of RT-PCR tests (verification the census of professionals and residents who have had the disease is explained in the previous paragraph). Each included professional will previously undergo RT-PCR tests to verify that they do not have the infection and are asymptomatic carriers.
4. That they give their consent to participate in the study and will not leave their job during the study follow-up for work reasons (unemployment, job change, etc.).

Para los residentes:
1. Personas institucionalizadas en residencias desde el inicio de la epidemia de COVID19 que no tienen la infección presente en el momento de entrar en el estudio. A este respecto, con anterioridad al primer día de valoración de cada residencia, se hará un censo de residentes y profesionales que ya han tenido COVID19 verificado por RT-PCR. Si el último residente o profesional ha tenido la enfermedad con una duración superior a 15 días, la residencia se excluirá del estudio. Una vez incluida la residencia (porque se ha confirmado la presencia de residentes y/o trabajadores expuestos a COVID19 hace menos de 15 días), la decisión de entrada en el estudio de cada sujeto participante se realizará solo mediante confirmación por RT-PCR basal, de acuerdo con las recomendaciones de la SEIMC sobre el uso de las pruebas de detección de anticuerpos en residencias de mayores21. Además, en tanto no se disponga de la PCR, se demorará la decisión de entrada en el estudio.
2. Que den su consentimiento para participar en el estudio o se obtenga de su representante/tutor legal (ver apartado de consentimiento informado).

Para los profesionales:
3. Profesionales asistenciales que no tienen la infección presente en el momento de entrar en el estudio, que prestan cuidado directo (AUXILIARES y enfermeras) a mayores institucionalizados con infección confirmada de COVID19 en los últimos 15 días mediante test de RT-PCR (la comprobación del censo de profesionales y residentes que han tenido la enfermedad se explica en el párrafo anterior). A cada profesional incluido se le realizará previamente test de RT-PCR para comprobar que no tiene la infección y es portador asintomático.
4. Que dan su consentimiento para participar en el estudio y no van a abandonar el empleo durante la celebración de los seguimientos del estudio por razones laborales (desempleo, cambio de trabajo, etc).

E.4

Principal exclusion criteria

a) Staff members who do not provide direct care to residents.
b) Residents with present or past SARS-CoV-2 infection, or with symptoms compatible with COVID19.
c) Staff members with present or past SARS-CoV-2 infection, or with symptoms compatible with COVID19.
d) Alterations of the QT interval or arrhythmias of any etiology. It will be verified by ECG and telematic transmission to the reference internist.
e) Presence of retinopathy of any etiology, changes in acuity or visual field.
f) Severe hearing loss (requires the use of hearing aids).
g) Structural heart disease.
h) History of non-structural heart failure, ischemic heart disease, SCASEST or SCACEST
i) Chronic liver disease.
j) Alcoholism.
k) Epilepsy.
l) For the participating professionals, pregnancy or suspected pregnancy (if they are planning pregnancy, or in fertilizer treatment, they must abandon the study).
m) Subjects with known HDQ hypersensitivity.
n) Subjects diagnosed with G6PDH deficiency.
o) Consumption of other medicines that prolong the QT: domperidone, ondansetron, cilostazol, antiarrhythmics (procainamide, amiodarone, flecainide, sotalol), macrolides (azithromycin, clarithromycin, erythromycin), quinolones (ciprofloxacin, levofloxacin), , neuroleptics (haloperidol, chlorpromazine, pimozide), antidepressants (citalopram, escitalopram), sulpiride, anticholinesterase drugs (donepezil). The possibility of withdrawal of any drug that could compromise the pharmacological management of psychotic disorders in older people with treatment of COVID infection19 will be evaluated using the criteria of the Consensus of Spanish Medical Societies the safety of co-administering HCQ and deciding on inclusion in the study. This process will be managed by the reference internists participating in the study.
p) Waiver to participate in the study

a) Miembros de la plantilla que no prestan cuidados directos a residentes.
b) Residentes con infección por SARS-CoV-2 presente o pasada, o con síntomas compatibles con COVID19.
c) Miembros de la plantilla con infección por SARS-CoV-2 presente o pasada, o con síntomas compatibles con COVID19.
d) Alteraciones del intervalo QT o arritmias de cualquier etiología. Se comprobará mediante ECG y transmisión telemática a internista de referencia.
e) Presencia de retinopatía de cualquier etiología alteraciones de la agudeza o del campo visual.
f) Hipoacusia severa (requiere uso de prótesis auditivas).
g) Cardiopatía estructural.
h) Antecedentes de insuficiencia cardiaca no estructural, cardiopatía isquémica, SCASEST o SCACEST
i) Hepatopatía crónica.
j) Alcoholismo.
k) Epilepsia.
l) Para las profesionales participantes, embarazo o sospecha de embarazo (si están planificando embarazo, o en tratamiento fertilizante, deberán abandonar el estudio).
m) Sujetos con hipersensibilidad a HDQ conocida.
n) Sujetos con diagnóstico de déficit de G6PDH.
o) Consumo de otros medicamentos que prolongan el QT: domperidona, ondansetrón, cilostazol, antiarrítmicos (procainamida, amiodarona, flecainida, sotalol), macrólidos (azitromicina, claritromicina, eritromicina), quinolonas (ciprofloxacino, levofloxacino, moxifloxacino), antifúngicos (fluconazol), neurolépticos (haloperidol, clorpromazina, pimozida), antidepresivos (citalopram, escitalopram), sulpiride, anticolinesterásicos (donepezilo). Se evaluará, mediante los criterios del Consenso de las SEMI, SEMFYC, SEPG, SEP, SEGG SEN y SEPB para el manejo farmacológico de trastornos psicóticos en personas mayores con tratamiento de la infección por COVID19, la posibilidad de retirada de algún fármaco que pudiera comprometer la seguridad de administración conjunta de HCQ y decidir la inclusión en el estudio. Este proceso estará gestionado por los internistas de referencia participantes en el estudio.
p) Renuncia a participar en el estudio

E.5 End points

E.5.1

Primary end point(s)

E.5.1.1

Timepoint(s) of evaluation of this end point

Days: 6, 14 and 28

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

Days: 6, 14 and 28

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

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)

Yes

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

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

Yes

E.8.1.7.1

Other trial design description

Clusters

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

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 último sujeto

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:

1930

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

1930

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

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

Perhaps some people in nursing homes might not be able to consent themselves

Quizás algunos residentes no puedan dar su consentimiento.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

1930

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1930

F.4.2.2

In the whole clinical trial

1930

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

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

2020-05-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-05-14

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

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