Clinical Trials Register

Summary
EudraCT Number:	2021-002298-25
Sponsor's Protocol Code Number:	20203331
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:	2021-07-27
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

2021-002298-25

A.3

Full title of the trial

A multicenter, adaptive, prospective, randomized trial evaluating the efficacy and safety of antithrombotic strategies in patients with COVID-19 following hospital discharge

Ensayo multicéntrico, adaptativo, prospectivo y aleatorizado que evalúa la eficacia y seguridad de las estrategias antitrombóticas en pacientes con COVID-19 después del alta hospitalaria.

A.3.1

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

COVID-19 Post-hospital Thrombosis Prevention Study

Estudio de prevención de trombosis poshospitalaria COVID-19

A.4.1

Sponsor's protocol code number

20203331

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 para la Investigación Biomédica del Hospital Universitario La Paz (FIBHULP)
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	National Institute of Neurological Disorders (NINDS), National Heart Lung and Blood Institute (NHLBI), National Institut
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	FIBHULP
B.5.2	Functional name of contact point	Rocío María Prieto Pérez
B.5.3	Address:
B.5.3.1	Street Address	Paseo de la Castellana 261
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28046
B.5.3.4	Country	Spain
B.5.4	Telephone number	+3491727 70 00
B.5.6	E-mail	rocioprieto.ucicec@gmail.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	APIXABAN
D.2.1.1.2	Name of the Marketing Authorisation holder	BRISTOL-MYERS SQUIBB, 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	APIXABAN
D.3.4	Pharmaceutical form	Film-coated 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	APIXABAN
D.3.9.3	Other descriptive name	eliquis
D.3.9.4	EV Substance Code	SUB25425
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	2.5
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	Film-coated 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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To determine the most effective and safe antithrombotic strategy to prevent the composite outcome of symptomatic deep vein thrombosis, pulmonary embolism, other venous thromboembolism, ischemic stroke, myocardial infarction, other arterial thromboembolism, and all-cause mortality by 30 days following discharge from the hospital.

Determinar la estrategia antitrombótica más eficaz y segura para prevenir el resultado combinado de trombosis venosa profunda sintomática, embolia pulmonar, otros tromboembolismos venosos, accidente cerebrovascular isquémico, infarto de miocardio, otros tromboembolismos arteriales y mortalidad por todas las causas a los 30 días después del alta hospitalaria. .

E.2.2

Secondary objectives of the trial

To determine the most effective and safe antithrombotic strategy on
(1) the endpoint of venous thromboembolism (inclusive of symptomatic deep vein thrombosis, pulmonary embolism, other venous thromboembolism) by 30 days in the study population;
(2) the endpoint of arterial thromboembolism (inclusive of ischemic stroke, myocardial infarction, other arterial thromboembolism) by 30 days in the study population;
(3) the composite primary outcome by 45 and 90 days following discharge from the hospital

Determinar la estrategia antitrombótica más eficaz y segura en
(1) el criterio de valoración de la tromboembolia venosa (incluida la trombosis venosa profunda sintomática, la embolia pulmonar y otras tromboembolias venosas) a los 30 días en la población de estudio;
(2) el criterio de valoración de tromboembolismo arterial (incluido accidente cerebrovascular isquémico, infarto de miocardio, otro tromboembolismo arterial) a los 30 días en la población de estudio; y
(3) el resultado primario compuesto a los 45 y 90 días después del alta hospitalaria

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age ≥ 18 years
• PCR-positive COVID-19 infection
• Hospitalized for 48 or more hours

• Edad ≥ 18 años
• Infección por COVID-19 positiva por PCR
• Hospitalizado durante 48 horas o más

E.4

Principal exclusion criteria

• Existing indication for anticoagulation, either therapeutic or prophylactic dose
• Contraindication to antithrombotic therapy, such as
a) ischemic stroke, intracranial bleed, or neurosurgery within 3 months
b) Known bleeding within the last 30 days requiring emergency room presentation of hospitalization
c) Known major surgery with 14 days (at least 1 hour and/or requires general anesthesia)
d) Inherited or acquired active bleeding disorder
• Platelet count < 50,000/mcL
• Hemoglobin < 8 gm/dL
• Renal insufficiency (eGFR < 30 mL/min/1.73 m2)
• Pregnancy
• Prison inmate
• Life expectancy less than 90 days
• Unwilling or unable to provide informed consent/unwilling or unable to complete the study protocol
• Dual antiplatelet therapy that cannot be discontinued
• Concomitant need for strong inducers/inhibitors of p-gp and CYP3A4

• Indicación existente de anticoagulación, ya sea en dosis terapéutica o profiláctica
• Contraindicaciones para la terapia antitrombótica, como
a) accidente cerebrovascular isquémico, hemorragia intracraneal o neurocirugía dentro de los 3 meses
b) Hemorragia conocida en los últimos 30 días que requiera hospitalización
c) Cirugía mayor conocida con 14 días (al menos 1 hora y / o requiere anestesia general)
d) Trastorno hemorrágico activo heredado o adquirido
• Recuento de plaquetas <50.000 / mcL
• Hemoglobina <8 g / dL
• Insuficiencia renal (TFGe <30 ml / min / 1,73 m2)
• El embarazo
• Recluso de prisión
• Esperanza de vida menor a 90 días
• No quiere o no puede dar su consentimiento informado / no quiere o no puede completar el protocolo del estudio
• Terapia antiplaquetaria dual que no se puede suspender
• Necesidad concomitante de inductores / inhibidores potentes de p-gp y CYP3A4

E.5 End points

E.5.1

Primary end point(s)

First occurrence of any of the components of the composite endpoint of symptomatic deep vein thrombosis, pulmonary embolism, other venous thromboembolism, ischemic stroke, myocardial infarction, other arterial thromboembolism, and all-cause mortality by 30 days post-discharge from the hospital

Primera aparición de cualquiera de los componentes del criterio de valoración combinado de trombosis venosa profunda sintomática, embolia pulmonar, otro tromboembolismo venoso, accidente cerebrovascular isquémico, infarto de miocardio, otro tromboembolismo arterial y mortalidad por todas las causas 30 días después del alta hospitalaria.

E.5.1.1

Timepoint(s) of evaluation of this end point

30 days post-discharge from the hospital

30 días después del alta hospitalaria.

E.5.2

Secondary end point(s)

(1) Venous thromboembolism (inclusive of symptomatic DVT of the upper or lower extremities, symptomatic and/or clinically relevant PE, and other symptomatic venous thrombosis, including cerebral sinus and splanchnic vein thrombosis) by 30 days post-discharge from the hospital;
(2) Arterial thromboembolism (inclusive of symptomatic ischemic stroke, myocardial infarction, and other symptomatic arterial thromboembolic events) by 30 days post-discharge from the hospital;
(3) the composite primary endpoint by 45 days and 90 days post-discharge from the hospital

(1) Tromboembolia venosa (incluida la TVP sintomática de las extremidades superiores o inferiores, EP sintomática y / o clínicamente relevante y otra trombosis venosa sintomática, incluida la trombosis del seno cerebral y la vena esplácnica) 30 días después del alta del hospital
(2) Tromboembolismo arterial (incluido accidente cerebrovascular isquémico sintomático, infarto de miocardio y otros eventos tromboembólicos arteriales sintomáticos) 30 días después del alta hospitalaria;
(3) el criterio de valoración principal compuesto a los 45 días y 90 días después del alta hospitalaria

E.5.2.1

Timepoint(s) of evaluation of this end point

(1) 30 days post-discharge from the hospital
(2) 30 days post-discharge from the hospital
(3) 45 days and 90 days post-discharge from the hospital

(1) 30 días después del alta hospitalaria
(2) 30 días después del alta hospitalaria
(3) a los 45 días y 90 días después del alta hospitalaria

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

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)

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

Yes

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Brazil

Canada

United States

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

Ultima visita del ultimo 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 years

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:

2660

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

2660

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