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Low Dose Anti-inflammatory Radiotherapy for the Treatment of Pneumonia by COVID-19

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ClinicalTrials.gov Identifier: NCT04380818
Recruitment Status : Recruiting
First Posted : May 8, 2020
Last Update Posted : June 18, 2020
Sponsor:
Collaborators:
Hospital Universitario Madrid Sanchinarro
Hospital del Mar
Hospital Universitari Sant Joan de Reus
Information provided by (Responsible Party):
Grupo de Investigación Clínica en Oncología Radioterapia

Study Description
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Brief Summary:

Low radiation doses produce anti-inflammatory effects, which may be useful in the treatment of respiratory complications of COVID-19. This type of treatment is non-invasive and therefore, a priori, it can be used in all types of patients.

Main objective: To evaluate the efficacy of low-dose lung irradiation as an adjunctive treatment in interstitial pneumonia in patients with COVID-19 by improving the PAFI O2 by 20% measured 48h after treatment with respect to the pre baseline measurement. -irradiation.


Condition or disease Intervention/treatment Phase
Pneumonia, Viral Radiation: Low-dose radiotherapy Drug: Hydroxychloroquine Sulfate Drug: Ritonavir/lopinavir Drug: Tocilizumab Injection [Actemra] Drug: Azithromycin Drug: Corticosteroid Drug: Low molecular weight heparin Device: Oxygen supply Not Applicable

Detailed Description:

Study design: This is a prospective multicenter study in 2 phases:

  1. Exploratory phase. It will include 10 patients, to assess the feasibility and efficacy of low-dose lung irradiation. If a minimum efficiency of 30% is not achieved, the study will not be continued.
  2. Comparative phase in two groups, a control group, which will only receive pharmacological treatment, and an experimental one. It will include 96 patients, the allocation will be 1: 2, that is, 32 in the control arm and 64 in the experimental arm, which will receive low-dose lung irradiation.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 106 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Low Dose Anti-inflammatory Radiotherapy for the Treatment of Pneumonia by COVID-19: Multi-central Prospective Study
Actual Study Start Date : June 5, 2020
Estimated Primary Completion Date : May 4, 2021
Estimated Study Completion Date : July 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Control group
a control group only receive pharmacological treatment
 Drug: Hydroxychloroquine Sulfate
200 mg/12h for 5 days
Other Name: Dolquine

Drug: Ritonavir/lopinavir
400/100 mg/12h for 7-10 days
Other Name: Kaletra

Drug: Tocilizumab Injection [Actemra]
600 mg/day for 1-2 doses
Other Name: Actemra

Drug: Azithromycin
500 mg/24h for 3 days

Drug: Corticosteroid
Corticosteroids (methylprednisolone/dexamethasone/prednisone)

Drug: Low molecular weight heparin
low molecular weight heparin (LMWH) in prophylaxis of venous thromboembolism

Device: Oxygen supply
Oxygen
Experimental: Experimental group
an experimental group will receive low-dose lung irradiation
 Radiation: Low-dose radiotherapy
Bilateral low-dose lung irradiation: 0.5 Gy in a single fraction. Optionally, additional 0.5 Gy fraction 48h later

Drug: Hydroxychloroquine Sulfate
200 mg/12h for 5 days
Other Name: Dolquine

Drug: Ritonavir/lopinavir
400/100 mg/12h for 7-10 days
Other Name: Kaletra

Drug: Tocilizumab Injection [Actemra]
600 mg/day for 1-2 doses
Other Name: Actemra

Drug: Azithromycin
500 mg/24h for 3 days

Drug: Corticosteroid
Corticosteroids (methylprednisolone/dexamethasone/prednisone)

Drug: Low molecular weight heparin
low molecular weight heparin (LMWH) in prophylaxis of venous thromboembolism

Device: Oxygen supply
Oxygen


Outcome Measures
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Primary Outcome Measures :
  1. Efficacy of low-dose pulmonary irradiation assessed by change in PAFI O2 by 20% [ Time Frame: Day 2 after interventional radiotherapy ]

    To evaluate the efficacy of low-dose pulmonary irradiation as an adjunctive treatment in interstitial pneumonia in patients with COVID-19 by improving the PAFI O2 by 20% measured 48h after treatment with respect to baseline pre-irradiation measurement. .

    In cases of impossibility the SaFiO2 will be determined



Secondary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: Day 30 and day 90 after interventional radiotherapy ]
    Lung toxicity measured according to CTCAEv5

  2. Change of the radiological image [ Time Frame: Days 7 and day 30 after interventional radiotherapy ]
    Chest CT

  3. Overall mortality [ Time Frame: Day 15 and Day 30 after interventional radiotherapy ]
    Death of any cause

  4. Measure of pro-inflammatory interleukins [ Time Frame: Days 1, day 4 and day 7 after interventional radiotherapy ]
    Interleukins IL-6, IL-10, IL-1, IL-2, IL-8 (pg/ml)

  5. Measure of trasforming growth factor (TGF-b) [ Time Frame: Days 1, day 4 and day 7 after interventional radiotherapy ]
    TGF-β (ng/ml)

  6. Measure of tumor necrosis factor alpha (TNF-a) [ Time Frame: Days 1, day 4 and day 7 after interventional radiotherapy ]
    TNF-α (pg/ml)

  7. Determining overexpression of pro-inflammatory selectin [ Time Frame: Days 1, day 4 and day 7 after interventional radiotherapy ]
    Overexpression of L-, E-, and P-selectin

  8. Determining cell adhesion molecules (CAMs) [ Time Frame: Days 1, day 4 and day 7 after interventional radiotherapy ]
    Overexpression of ICAM-1, VCAM

  9. Measure of marker of oxidative stress PON-1 [ Time Frame: Days 1, day 4 and day 7 after interventional radiotherapy ]
    PON-1(paraoxonase and arylesterase activity) (IU/ml)


Eligibility Criteria
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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 to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >=18 years old
  • Moderate to severe COVID-19 pneumonia with fewer than 8 days of symptom onset and currently receiving standard medication for COVID-19 at appropriate doses
  • PAFIO2 of less than 300 mmHg or SaFI02 <315 mmHg
  • Patients who are not candidates for admission to the Intensive Care Unit due to age, concomitant diseases or general condition.

  • One of the following conditions:

    • or IL6 greater than 40

    • or PCR> 100mg / l

      • D-dimer greater than 1500ng / ml
      • Suspected cytokine release syndrome
  • Have read the information sheet and signed the informed consent

Exclusion Criteria:

  • Age <18 years
  • Failure to meet the inclusion criteria
  • Leukopenia <1000
  • Pregnancy
  • Not understanding or refusing the purpose of the study
Contacts and Locations
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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): NCT04380818


Contacts
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Contact: ANGEL MONTERO, Md, PhD +34667767601 angel.monteroluis@gmail.com

Locations
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Spain
Hospital Sant Joan de Reus Not yet recruiting
Reus, Tarragona, Spain, 43204
Contact: MERITXELL ARENAS, MD, PhD       meritxell.arenas@gmail.com   
Hospital Del Mar Not yet recruiting
Barcelona, Spain, 08003
Contact: MANEL ALGARA, MD, PhD       MAlgara@parcdesalutmar.cat   
Hospital Universitario Madrid Sanchinarro Recruiting
Madrid, Spain, 28050
Contact: Angel Montero, MD, PhD    +34915629949    amontero@hmhospitales.com   
Sponsors and Collaborators
Grupo de Investigación Clínica en Oncología Radioterapia
Hospital Universitario Madrid Sanchinarro
Hospital del Mar
Hospital Universitari Sant Joan de Reus
Investigators
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Principal Investigator: Angel Montero, MD, PhD Hospital Universitario Madrid Sanchinarro
Principal Investigator: Manel Algara, MD, PhD Hospital del Mar
Principal Investigator: Merirxell Arenas, MD, PhD Hospital Universitario Sant Joan de Reus
More Information
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Publications:
Jean-Marc Cosset, Éric Deutsch, Louis Bazire, Jean-Jacques Mazeron, Cyrus Chargari, Irradiation pulmonaire à faible dose pour l'orage de cytokines du covid-19: pourquoi pas?, Cancer/Radiothérapie, 2020, , ISSN 1278-3218, https://doi.org/10.1016/j.canrad.2020.04.003.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Grupo de Investigación Clínica en Oncología Radioterapia
ClinicalTrials.gov Identifier: NCT04380818    
Other Study ID Numbers: IPACOVID
First Posted: May 8, 2020    Key Record Dates
Last Update Posted: June 18, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual epidemiological and clinical data will be shared after recruitment is complete.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Protocol/ICF from approval Individual epidemiological and clinical data after recruitment is complete.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Grupo de Investigación Clínica en Oncología Radioterapia:
COVID 19
RADIATION
Anti-inflammatory effects
Additional relevant MeSH terms:
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Pneumonia, Viral
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Virus Diseases
Ritonavir
Lopinavir
Azithromycin
Hydroxychloroquine
Heparin
Heparin, Low-Molecular-Weight
Tinzaparin
Dalteparin
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
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Anti-Bacterial Agents
Antimalarials
Antiprotozoal Agents