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

Primary Purpose

Pneumonia, Viral

Status
Unknown status
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Low-dose radiotherapy
Hydroxychloroquine Sulfate
Ritonavir/lopinavir
Tocilizumab Injection [Actemra]
Azithromycin
Corticosteroid
Low molecular weight heparin
Oxygen supply
Sponsored by
Grupo de Investigación Clínica en Oncología Radioterapia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Pneumonia, Viral focused on measuring COVID 19, RADIATION, Anti-inflammatory effects

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hospital Sant Joan de Reus
  • Hospital Del Mar
  • Hospital Universitario Madrid SanchinarroRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control group

Experimental group

Arm Description

a control group only receive pharmacological treatment

an experimental group will receive low-dose lung irradiation

Outcomes

Primary Outcome Measures

Efficacy of low-dose pulmonary irradiation assessed by change in PAFI O2 by 20%
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

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Lung toxicity measured according to CTCAEv5
Change of the radiological image
Chest CT
Overall mortality
Death of any cause
Measure of pro-inflammatory interleukins
Interleukins IL-6, IL-10, IL-1, IL-2, IL-8 (pg/ml)
Measure of trasforming growth factor (TGF-b)
TGF-β (ng/ml)
Measure of tumor necrosis factor alpha (TNF-a)
TNF-α (pg/ml)
Determining overexpression of pro-inflammatory selectin
Overexpression of L-, E-, and P-selectin
Determining cell adhesion molecules (CAMs)
Overexpression of ICAM-1, VCAM
Measure of marker of oxidative stress PON-1
PON-1(paraoxonase and arylesterase activity) (IU/ml)

Full Information

First Posted
May 4, 2020
Last Updated
July 29, 2021
Sponsor
Grupo de Investigación Clínica en Oncología Radioterapia
Collaborators
Hospital Universitario Madrid Sanchinarro, Hospital del Mar, Hospital Universitari Sant Joan de Reus
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1. Study Identification

Unique Protocol Identification Number
NCT04380818
Brief Title
Low Dose Anti-inflammatory Radiotherapy for the Treatment of Pneumonia by COVID-19
Official Title
Low Dose Anti-inflammatory Radiotherapy for the Treatment of Pneumonia by COVID-19: Multi-central Prospective Study
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Unknown status
Study Start Date
June 5, 2020 (Actual)
Primary Completion Date
September 4, 2021 (Anticipated)
Study Completion Date
November 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Grupo de Investigación Clínica en Oncología Radioterapia
Collaborators
Hospital Universitario Madrid Sanchinarro, Hospital del Mar, Hospital Universitari Sant Joan de Reus

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumonia, Viral
Keywords
COVID 19, RADIATION, Anti-inflammatory effects

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
106 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control group
Arm Type
Active Comparator
Arm Description
a control group only receive pharmacological treatment
Arm Title
Experimental group
Arm Type
Experimental
Arm Description
an experimental group will receive low-dose lung irradiation
Intervention Type
Radiation
Intervention Name(s)
Low-dose radiotherapy
Intervention Description
Bilateral low-dose lung irradiation: 0.5 Gy in a single fraction. Optionally, additional 0.5 Gy fraction 48h later
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine Sulfate
Other Intervention Name(s)
Dolquine
Intervention Description
200 mg/12h for 5 days
Intervention Type
Drug
Intervention Name(s)
Ritonavir/lopinavir
Other Intervention Name(s)
Kaletra
Intervention Description
400/100 mg/12h for 7-10 days
Intervention Type
Drug
Intervention Name(s)
Tocilizumab Injection [Actemra]
Other Intervention Name(s)
Actemra
Intervention Description
600 mg/day for 1-2 doses
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Intervention Description
500 mg/24h for 3 days
Intervention Type
Drug
Intervention Name(s)
Corticosteroid
Intervention Description
Corticosteroids (methylprednisolone/dexamethasone/prednisone)
Intervention Type
Drug
Intervention Name(s)
Low molecular weight heparin
Intervention Description
low molecular weight heparin (LMWH) in prophylaxis of venous thromboembolism
Intervention Type
Device
Intervention Name(s)
Oxygen supply
Intervention Description
Oxygen
Primary Outcome Measure Information:
Title
Efficacy of low-dose pulmonary irradiation assessed by change in PAFI O2 by 20%
Description
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
Time Frame
Day 2 after interventional radiotherapy
Secondary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Description
Lung toxicity measured according to CTCAEv5
Time Frame
Day 30 and day 90 after interventional radiotherapy
Title
Change of the radiological image
Description
Chest CT
Time Frame
Days 7 and day 30 after interventional radiotherapy
Title
Overall mortality
Description
Death of any cause
Time Frame
Day 15 and Day 30 after interventional radiotherapy
Title
Measure of pro-inflammatory interleukins
Description
Interleukins IL-6, IL-10, IL-1, IL-2, IL-8 (pg/ml)
Time Frame
Days 1, day 4 and day 7 after interventional radiotherapy
Title
Measure of trasforming growth factor (TGF-b)
Description
TGF-β (ng/ml)
Time Frame
Days 1, day 4 and day 7 after interventional radiotherapy
Title
Measure of tumor necrosis factor alpha (TNF-a)
Description
TNF-α (pg/ml)
Time Frame
Days 1, day 4 and day 7 after interventional radiotherapy
Title
Determining overexpression of pro-inflammatory selectin
Description
Overexpression of L-, E-, and P-selectin
Time Frame
Days 1, day 4 and day 7 after interventional radiotherapy
Title
Determining cell adhesion molecules (CAMs)
Description
Overexpression of ICAM-1, VCAM
Time Frame
Days 1, day 4 and day 7 after interventional radiotherapy
Title
Measure of marker of oxidative stress PON-1
Description
PON-1(paraoxonase and arylesterase activity) (IU/ml)
Time Frame
Days 1, day 4 and day 7 after interventional radiotherapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
ANGEL MONTERO, Md, PhD
Phone
+34667767601
Email
angel.monteroluis@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Angel Montero, MD, PhD
Organizational Affiliation
Hospital Universitario Madrid Sanchinarro
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Manel Algara, MD, PhD
Organizational Affiliation
Hospital del Mar
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Merirxell Arenas, MD, PhD
Organizational Affiliation
Hospital Universitario Sant Joan de Reus
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Sant Joan de Reus
City
Reus
State/Province
Tarragona
ZIP/Postal Code
43204
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
MERITXELL ARENAS, MD, PhD
Email
meritxell.arenas@gmail.com
Facility Name
Hospital Del Mar
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
MANEL ALGARA, MD, PhD
Email
MAlgara@parcdesalutmar.cat
Facility Name
Hospital Universitario Madrid Sanchinarro
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Angel Montero, MD, PhD
Phone
+34915629949
Email
amontero@hmhospitales.com

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual epidemiological and clinical data will be shared after recruitment is complete.
IPD Sharing Time Frame
Protocol/ICF from approval Individual epidemiological and clinical data after recruitment is complete.
Citations:
PubMed Identifier
32171193
Citation
Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I, Kritas SK. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020 March-April,;34(2):327-331. doi: 10.23812/CONTI-E.
Results Reference
background
PubMed Identifier
23057008
Citation
Rodel F, Frey B, Manda K, Hildebrandt G, Hehlgans S, Keilholz L, Seegenschmiedt MH, Gaipl US, Rodel C. Immunomodulatory properties and molecular effects in inflammatory diseases of low-dose x-irradiation. Front Oncol. 2012 Sep 25;2:120. doi: 10.3389/fonc.2012.00120. eCollection 2012.
Results Reference
background
PubMed Identifier
22907572
Citation
Arenas M, Sabater S, Hernandez V, Rovirosa A, Lara PC, Biete A, Panes J. Anti-inflammatory effects of low-dose radiotherapy. Indications, dose, and radiobiological mechanisms involved. Strahlenther Onkol. 2012 Nov;188(11):975-81. doi: 10.1007/s00066-012-0170-8. Epub 2012 Aug 22.
Results Reference
background
PubMed Identifier
18031855
Citation
Arenas M, Gil F, Gironella M, Hernandez V, Biete A, Pique JM, Panes J. Time course of anti-inflammatory effect of low-dose radiotherapy: correlation with TGF-beta(1) expression. Radiother Oncol. 2008 Mar;86(3):399-406. doi: 10.1016/j.radonc.2007.10.032. Epub 2007 Nov 26.
Results Reference
background
PubMed Identifier
22545750
Citation
Lodermann B, Wunderlich R, Frey S, Schorn C, Stangl S, Rodel F, Keilholz L, Fietkau R, Gaipl US, Frey B. Low dose ionising radiation leads to a NF-kappaB dependent decreased secretion of active IL-1beta by activated macrophages with a discontinuous dose-dependency. Int J Radiat Biol. 2012 Oct;88(10):727-34. doi: 10.3109/09553002.2012.689464. Epub 2012 May 22.
Results Reference
background
PubMed Identifier
24348219
Citation
Calabrese EJ, Dhawan G. How radiotherapy was historically used to treat pneumonia: could it be useful today? Yale J Biol Med. 2013 Dec 13;86(4):555-70.
Results Reference
background
PubMed Identifier
31060383
Citation
Calabrese EJ, Dhawan G, Kapoor R, Kozumbo WJ. Radiotherapy treatment of human inflammatory diseases and conditions: Optimal dose. Hum Exp Toxicol. 2019 Aug;38(8):888-898. doi: 10.1177/0960327119846925. Epub 2019 May 6.
Results Reference
background
PubMed Identifier
32342871
Citation
Kirkby C, Mackenzie M. Is low dose radiation therapy a potential treatment for COVID-19 pneumonia? Radiother Oncol. 2020 Jun;147:221. doi: 10.1016/j.radonc.2020.04.004. Epub 2020 Apr 6. No abstract available.
Results Reference
background
Citation
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.
Results Reference
background
PubMed Identifier
32437820
Citation
Dhawan G, Kapoor R, Dhawan R, Singh R, Monga B, Giordano J, Calabrese EJ. Low dose radiation therapy as a potential life saving treatment for COVID-19-induced acute respiratory distress syndrome (ARDS). Radiother Oncol. 2020 Jun;147:212-216. doi: 10.1016/j.radonc.2020.05.002. Epub 2020 May 8.
Results Reference
background
PubMed Identifier
32613089
Citation
Algara M, Arenas M, Marin J, Vallverdu I, Fernandez-Leton P, Villar J, Fabrer G, Rubio C, Montero A. Low dose anti-inflammatory radiotherapy for the treatment of pneumonia by covid-19: A proposal for a multi-centric prospective trial. Clin Transl Radiat Oncol. 2020 Jun 15;24:29-33. doi: 10.1016/j.ctro.2020.06.005. eCollection 2020 Sep.
Results Reference
derived

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

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