Clinical Trials Register

Summary
EudraCT Number:	2020-001548-24
Sponsor's Protocol Code Number:	BEMICOVID-19
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-07-22
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

2020-001548-24

A.3

Full title of the trial

A randomized, single-blind study with a parallel control group on the efficacy and safety of bemiparin at therapeutic dose vs. prophylactic dose in patients hospitalized for COVID-19

Estudio aleatorizado, simple ciego, con grupo control paralelo sobre la eficacia y seguridad de bemiparina a dosis terapéutica vs. dosis profiláctica en pacientes hospitalizados por COVID-19

A.3.1

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

Clinical trial on the efficacy and safety of bemiparin in patients hospitalized because of COVID-19

Ensayo clínico en pacientes hospitalizados por COVID-19 sobre la eficacia y seguridad de bemiparina

A.4.1

Sponsor's protocol code number

BEMICOVID-19

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	Fundación de Investigación HM Hospitales
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	LABORATORIOS FARMACÉUTICOS ROVI, S.A.
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	Fundación de investigación de HM Hospitales
B.5.2	Functional name of contact point	Secretaría
B.5.3	Address:
B.5.3.1	Street Address	Plaza Conde Valle de Suchil, 2
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28015
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34917567984
B.5.6	E-mail	secretaria@fundacionhm.com

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	HIBOR 5.000 UI anti –Xa/0,2 ml solución inyectable en jeringas precargadas
D.2.1.1.2	Name of the Marketing Authorisation holder	LABORATORIOS FARMACÉUTICOS ROVI, 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.3.1	Product name	Bemiparina sódica
D.3.4	Pharmaceutical form	Solution for infusion in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BEMIPARIN SODIUM
D.3.9.1	CAS number	9041-08-1
D.3.9.4	EV Substance Code	SUB20549
D.3.10	Strength
D.3.10.1	Concentration unit	IU/kg international unit(s)/kilogram
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	115
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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

COVID-19 infection

Infección por COVID-19

E.1.1.1

Medical condition in easily understood language

COVID-19 infection

Infección por 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	LLT
E.1.2	Classification code	10084382
E.1.2	Term	Coronavirus disease 2019
E.1.2	System Organ Class	10021881 - Infections and infestations

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	10051905
E.1.2	Term	Coronavirus infection
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10070255
E.1.2	Term	Coronavirus test positive
E.1.2	System Organ Class	10022891 - Investigations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.0
E.1.2	Level	HLT
E.1.2	Classification code	10084510
E.1.2	Term	Coronavirus infections
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 assess the effect of bemiparin at therapeutic dose vs. prophylactic dose in the early evolution of hospitalized patients with COVID-19.

Evaluar el efecto de bemiparina a dosis terapéutica vs. dosis profiláctica en la evolución temprana de los pacientes hospitalizados con COVID-19.

E.2.2

Secondary objectives of the trial

-Evaluate differences in clinical, radiological and ventilatory parameters between the two arms of the study.
-Evaluate the safety of bemiparin at therapeutic and prophylactic doses in this group of patients.

-Evaluar diferencias en parámetros clinicos, radiológicos y ventilatorios entre los dos brazos del estudio.
-Evaluar la seguridad de bemiparina a dosis terapéutica y profiláctica en este grupo de pacientes.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Informed consent.
2. Age of 18 years or more.
3. Patient with suspected COVID-19 and who meets hospitalization criteria.
4. D-dimer> 500 ng / ml.
5. Clinical characteristics highly compatible with SARS-CoV-2 infection and confirmation by RT-qPCR at baseline or in the second sample in case of a first negative test and clinical suspicion remains.
6. Patient admitted to hospital

1. Consentimiento informado.
2. Edad de 18 años o más.
3. Paciente con sospecha de COVID-19 y que cumpla criterios de hospitalización.
4. Dímero-D >500 ng/ml.
5. Características clínicas altamente compatibles con infección por SARS-CoV-2 y confirmación mediante RT-qPCR basal o en segunda muestra en caso de una primera negativa y persista la sospecha clínica.
6. Paciente ingresado en el hospital

E.4

Principal exclusion criteria

1. ICU admission criteria.
2. Pregnancy.
3. Creatine clearance <30 ml / min (Cockroft-Gault).
4. Severe liver or pancreatic function disorder.
5. Acute bacterial endocarditis and slow endocarditis.
6. Patient previously anticoagulated (although it is allowed to have received heparin at a previous low dose without time limit).
7. Patient with high hemorrhagic risk due to previous medical-surgical history.
8. Severe thrombocytopenia (<80,000 platelets / mm3) or known history of heparin-induced thrombocytopenia.
9. Active bleeding or increased risk of bleeding from haemostasis disorders or from organic lesions that are liable to bleed (eg, active peptic ulcer, hemorrhagic stroke, aneurysms, or brain malignancies).
10. Damage or surgical interventions in the central nervous system, eyes and ears that have taken place in the last 2 months.
11. Simultaneous participation in another clinical trial that could have a conflictive interaction with what it is intended to evaluate.
12. Any situation that in the opinion of the researcher could interfere with the treatment or with the evolution of the patient.

1. Criterios de ingreso en UCI.
2. Embarazo.
3. Aclaramiento de creatinia <30 ml/min (Cockroft-Gault).
4. Trastorno grave de la función hepática o pancreática.
5. Endocarditis bacteriana aguda y endocarditis lenta.
6. Paciente previamente anticoagulado (aunque se permite haber recibido heparina a dosis baja previa sin límite de tiempo).
7. Paciente con alto riesgo hemorrágico por antecedentes médico-quirúrgicos previos.
8. Trombocitopenia grave (< 80.000 plaquetas/mm3) o antecedentes conocidos de trombocitopenia inducida por heparina.
9. Hemorragia activa o incremento del riesgo de sangrado por alteraciones de la hemostasia o por lesiones orgánicas susceptibles de sangrar (ej.: úlcera péptica activa, accidente cerebrovascular hemorrágico, aneurismas o neoplasias cerebrales).
10. Daños o intervenciones quirúrgicas en el sistema nervioso central, ojos y oídos que hayan tenido lugar en los últimos 2 meses.
11. Participación simultánea en otro ensayo clínico que pudiera tener una interacción conflictiva con lo que en éste se pretende evaluar.
12. Cualquier situación que a juicio del investigador pudiera interferir con el tratamiento o con la evolución del paciente.

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients with any of the following in the combined worsening variable on day 10 +/- 1:
1. Death.
2. ICU admission.
3. Need for either non-invasive or invasive mechanical ventilation.
4. Progression to moderate / severe respiratory distress syndrome according to objective criteria (Berlin definition).
5. Venous thromboembolism (deep vein thrombosis or pulmonary embolism) or arterial (acute myocardial infarction or stroke).

Proporción de pacientes que en la variable combinada de empeoramiento el día 10 +/-1 presenten alguno de los siguientes:
1. Muerte.
2. Ingreso en UCI.
3. Necesidad de ventilación mecánica ya sea no invasiva o invasiva.
4. Progresión a síndrome de distress respiratorio moderado/grave según criterios objetivos (Definición de Berlín).
5. Tromboembolismo venoso (thrombosis venosa profunda o embolismo pulmonar) o arterial (infarto agudo de miocardio o ictus).

E.5.1.1

Timepoint(s) of evaluation of this end point

day 10 +/-1

día 10 +/-1

E.5.2

Secondary end point(s)

1. 28-day mortality from any cause.
2. Proportion of subjects that requires admission to the ICU.
3. Proportion of subjects requiring non-invasive mechanical ventilation.
4. Proportion of subjects requiring invasive mechanical ventilation.
5. Proportion of subjects with some organ failure.
6. Proportion of patients who have modified their oxygen therapy requirements between treatment assessment visit and baseline.
7. Proportion of subjects with pathological angioTAC on day 10 ± 1.
8. Proportion of subjects with improvement in chest radiography on day 10 ± 1.
9. Proportion and median hospital discharge between patients in both groups.
10. D-dimer modification, ferritin, titration scores.
11. Adverse events (total and serious).
12. Related adverse events (total and serious).
13. Clinically relevant major and non major hemorrhages.

1. Mortalidad a los 28 días por cualquier causa.
2. Proporción de sujetos que requiere de ingreso en UCI.
3. Proporción de sujetos que requiere de ventilación mecánica no invasiva.
4. Proporción de sujetos que requiere de ventilación mecánica invasiva.
5. Proporción de sujetos con algún fracaso de órgano.
6. Proporción de pacientes que han modificado sus requisitos de oxigenoterapia entre visita de valoración del tratamiento y basal.
7. Proporción de sujetos con angioTAC patológico el día 10±1.
8. Proporción de sujetos con mejoría en radiografía de tórax el día 10±1.
9. Proporción y mediana alta hospitalaria entre pacientes de ambos grupos.
10. Modificación del dímero-D, ferritina, scores de valoración.
11. Acontecimientos adversos (totales y graves).
12. Acontecimientos adversos relacionados (totales y graves).
13. Hemorragias mayores y no mayores clínicamente relevantes.

E.5.2.1

Timepoint(s) of evaluation of this end point

Through the study, Day 10 and Day 28

A lo largo del estudio, Día 10, Día 28

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

E.8.1.3

Single blind

Yes

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

Bemiparina a dosis profiláctica

Bemiparin at prohylactic dose

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

Last Subject Last Visit

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

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2020-07-22.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

Yes

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

Consentimiento oral debido a la crisis sanitaria y posterior ratificación por escrito del consentimiento oral, cuando las circunstancias lo permitan

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

120

F.4.2

For a multinational trial

F.4.2.1

In the EEA

120

F.4.2.2

In the whole clinical trial

120

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)

Ninguno - no procede

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

2020-06-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-05-28

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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