Clinical trial NCT04380818: 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
Overall status: UNKNOWN
Phase: NA
Conditions: Pneumonia, Viral
Keywords: COVID 19
RADIATION
Anti-inflammatory effects
Lead sponsor: Grupo de Investigación Clínica en Oncología Radioterapia
Sponsor class: OTHER
Collaborators: name: Hospital Universitario Madrid Sanchinarro
name: Hospital del Mar
name: Hospital Universitari Sant Joan de Reus
First posted: 2020-05-08
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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:

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.

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

Primary outcomes:
measure: Efficacy of low-dose pulmonary irradiation assessed by change in PAFI O2 by 20%
timeFrame: Day 2 after interventional radiotherapy
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: Day 30 and day 90 after interventional radiotherapy
measure: Change of the radiological image
timeFrame: Days 7 and day 30 after interventional radiotherapy
measure: Overall mortality
timeFrame: Day 15 and Day 30 after interventional radiotherapy
measure: Measure of pro-inflammatory interleukins
timeFrame: Days 1, day 4 and day 7 after interventional radiotherapy
measure: Measure of trasforming growth factor (TGF-b)
timeFrame: Days 1, day 4 and day 7 after interventional radiotherapy
measure: Measure of tumor necrosis factor alpha (TNF-a)
timeFrame: Days 1, day 4 and day 7 after interventional radiotherapy
measure: Determining overexpression of pro-inflammatory selectin
timeFrame: Days 1, day 4 and day 7 after interventional radiotherapy
measure: Determining cell adhesion molecules (CAMs)
timeFrame: Days 1, day 4 and day 7 after interventional radiotherapy
measure: Measure of marker of oxidative stress PON-1
timeFrame: Days 1, day 4 and day 7 after interventional radiotherapy
Other outcomes:
Locations:
city: Reus
country: Spain
facility: Hospital Sant Joan de Reus
state: Tarragona
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
Study officials:
affiliation: Hospital Universitario Madrid Sanchinarro
name: Angel Montero, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital del Mar
name: Manel Algara, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Sant Joan de Reus
name: Merirxell Arenas, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.