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Clinical Trial to Evaluate Efficacy of 3 Types of Treatment in Patients With Pneumonia by COVID-19 (Covid-19HUF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04346147
Recruitment Status : Recruiting
First Posted : April 15, 2020
Last Update Posted : May 8, 2020
Sponsor:
Collaborator:
Centro Nacional de Investigaciones Oncologicas CARLOS III
Information provided by (Responsible Party):
Hospital Universitario de Fuenlabrada

Brief Summary:

In absence of vaccine and medications specifically designed to treat SARS-CoV-2 disease, identifying treatment options is critical at this time to control the disease outbreak.

For this, we have designed a phase II trial of efficacy and safety with 3 branches of different combinations of treatment to identify which is the best early treatment option for patients with pneumonia due to SARS-CoV-2 (Covid-19) Identifying treatment options as early as possible is critical to the SARS-CoV-2 outbreak response. Currently, there is no approved vaccine for the disease and the treatments being used are not specifically designed for the SARS-CoV-2 virus, but are different groups of drugs used for other pathologies with mechanisms of action that justify their use because they inhibit entry of the virus into virus cells or proteases.

The study aims to compare lopinavir / ritonavir (200 /50), imatinib 400mg, baricitinib 4mg, in combination with hydroxychloroquine 200mg, administered for 7 days in the setting of SARS-CoV-2 pneumonia treatment.

Patients who meet inclusion criteria and do not have any exclusion criteria will be randomized to receive open treatment 1:1:1


Condition or disease Intervention/treatment Phase
COVID-19 Pneumonia Drug: Hidroxicloroquine Drug: Lopinavir/ritonavir Drug: Imatinib tablets Drug: Baricitinib Oral Tablet Phase 2

Detailed Description:

Identifying treatment options is critical to the SARS-CoV-2 outbreak response. Currently there is no vaccine and treatments used are not specifically designed for this virus; They are drugs used for other pathologies. We have identified possible drugs with a known safety profile, selected the most promising ones and designed 3 combinations to select the one with the best results in clinical improvement of pneumonia due to Covid-19.

-Virus entry inhibitors: broad spectrum antivirals (antimalarials). They block viral infection by increasing endosomal pH necessary for virus / cell fusion, as well as interfering with glycosylation of cellular SARS-CoV receptors. It also has immunomodulatory activity, which can enhance antiviral effect. Hydroxychloroquine more powerful than chloroquine.

Baricitinib, Janus kinase inhibitor, showing high affinity for AAK1. Disruption of AAK1 (one of the known regulators of viral endocytosis) could block passage of SARS-CoV-2 to cells and also the intracellular assembly of virus particles. Furthermore, it has the capacity to bind cyclin G-associated kinase, another regulator of endocytosis. You can limit systemic inflammatory response and cytokine production by inhibiting the JAK-STAT32 pathway.

Imatinib; Antitumor agent inhibitory activity of some tirsin kinases (TK), especially fusion oncoprotein BCR-ABL1, c-kit and native kinase ABL1. It has shown antiviral properties in early stages of infection against SARS-CoV and MERS-CoV, phylogenetically related to SARS-CoV2. In addition, it has been linked to reduced inflammation and improved endothelial barrier and pulmonary edema.

-Protease inhibitors: lopinavir / ritonavir (HIV treatment); expected interactions with SARS-CoV-2 proteases; The therapeutic effect of ritonavir and lopinavir could be mainly due to its inhibitory effect on coronavirus endopeptidase C30.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 165 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective, Phase II, Randomized, Open-label, Parallel Group Study to Evaluate the Efficacy of Hydroxychloroquine Together With Baricitinib, Imatinib or Early Lopinavir / Ritonavir in Patients With SARS Cov2 Pneumonia
Actual Study Start Date : April 13, 2020
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Experimental: Lopinavir/ Ritonavir 400 mg
Hidroxicloroquina 200mg 1 tablet every 12 hours Lopinavir/ Ritonavir 200/50 mg 1 tablet 12 hours
Drug: Hidroxicloroquine
Hidroxicloroquine 200 mg BID oral
Other Name: Dolquine

Drug: Lopinavir/ritonavir
Lopinavir/ritonavir 200/50 mg BID oral
Other Name: Best care

Experimental: Imatinib 400 mg
Hidroxicloroquina 200mg 1 tablet every 12 hours Imatinib 400 mg 1 tablet 24 hours
Drug: Hidroxicloroquine
Hidroxicloroquine 200 mg BID oral
Other Name: Dolquine

Drug: Imatinib tablets
Imatinib 400 mg QD oral
Other Name: Arm A

Experimental: Baricitinib 4 mg
Hidroxicloroquina 200mg 1 tablet every 12 hours Baricitinib 4 mg 1 tablet 24 hours
Drug: Hidroxicloroquine
Hidroxicloroquine 200 mg BID oral
Other Name: Dolquine

Drug: Baricitinib Oral Tablet
Baricitinib 4 mg QD oral
Other Name: Arm B




Primary Outcome Measures :
  1. time to clinical improvement [ Time Frame: baseline to day 14 ]
    time from inclusion to improvement by 2 points on the "seven-category ordinal scale" or high, whichever comes first


Secondary Outcome Measures :
  1. Safety of treatments [ Time Frame: through study completion, an average of 1 month ]
    number of serious adverse effects and premature discontinuation of treatment

  2. Tolerability of treatments [ Time Frame: during treatment and up to 30 days after the last treatment dose ]
    Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0


Other Outcome Measures:
  1. Biomarkers and genetic markers of susceptibility to SARS-CoV-2 [ Time Frame: baseline ]
    Possible biomarkers and genetic markers of susceptibility to SARS-CoV-2 using high-performance techniques with serum DNA from the participants



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent form
  • ≥18 years
  • Confirmed diagnosis Pneumonia Covid19 positive
  • ECOG functional state 0 or 1
  • Less than 7 days from onset of symptoms saw.
  • NO contraindication for medication
  • ECG QT <0.4
  • Adequate liver, kidney and hematological function (or within the safety range to use these drugs):

    1. Absolute granulocyte count> 1.5 x 109 / L
    2. Absolute platelet count> 100 x 109 / L
    3. Hb> 10 g / dL
    4. Cr <1.5 mg / dL or Clearance> 50mL / min
    5. Bilirubin <3 ULN 6. AST / ALT ≤ 2.5 times ULN

Exclusion Criteria:

  • No Covid confirmation
  • No pneumonia
  • Previous treatment with any of the study drugs
  • Concomitant serious medical condition:

    1. Congestive Heart failure
    2. Acute myocardial infarction 6 months prior
    3. Unstable Angina
    4. Cardiomyopathy
    5. Unstable Ventricular Arrhythmia
    6. Uncontrolled Hypertension
    7. Uncontrolled psychotic disorders
    8. Serious active infections
    9. HIV infections
    10. Active hepatitis
    11. Neoplasia in active cancer treatment
  • Inability to take oral medication or malabsorption syndrome saw.
  • Inability to comply with study and follow-up procedures
  • History of only relevant thromboembolic or hemorrhagic episodes in the last 6 months
  • Contraindication to any study medication
  • Pregnant women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04346147


Contacts
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Contact: David Bernal, Ph MD +34916006180 david.bernal@salud.madrid.org
Contact: Berta Nasarre, Pharmacist +34916006584 bnasarre@ext.cnio.es

Locations
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Spain
Hospital Universitario de Fuenlabrada Recruiting
Fuenlabrada, Madrid, Spain, 28942
Contact: David Bernal, Ph MD    +34916006180    david.bernal@salud.madrid.org   
Contact: Juan Victor San Martin, Ph    +34916006180    juanvictor.san@salud.madrid.org   
Principal Investigator: David Bernal, Ph MD         
Sub-Investigator: Juan Victor San Martín, Ph         
Sub-Investigator: Diego Malon, Ph         
Sub-Investigator: Mario García Gil, PharmD         
Sub-Investigator: Berta Nasarre López, Pharm         
Sub-Investigator: Belén Hernández Muniesa, Pharm         
Sub-Investigator: Alicia Algaba, BS MD         
Sub-Investigator: Fernando Bermejo, Ph MD         
Sub-Investigator: Miguel Urioste, Ph MD         
Sponsors and Collaborators
Hospital Universitario de Fuenlabrada
Centro Nacional de Investigaciones Oncologicas CARLOS III
Investigators
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Principal Investigator: David Bernal, Ph MD Hospital Universitario de Fuenlabrada
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Responsible Party: Hospital Universitario de Fuenlabrada
ClinicalTrials.gov Identifier: NCT04346147    
Other Study ID Numbers: 24032020
First Posted: April 15, 2020    Key Record Dates
Last Update Posted: May 8, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Ritonavir
Lopinavir
Hydroxychloroquine
Imatinib Mesylate
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antineoplastic Agents
Protein Kinase Inhibitors
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Antirheumatic Agents