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

Pneumonia, Viral Clinical Trial

Official title:

Low Dose Anti-inflammatory Radiotherapy for the Treatment of Pneumonia by COVID-19: Multi-central Prospective Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04380818
• Other study ID #: IPACOVID
• Status: Recruiting
• Phase: N/A
• Start date: June 5, 2020
• Est. completion date: November 1, 2021

Study information

• Verified date: July 2021
• Source: Grupo de Investigación Clínica en Oncología Radioterapia
• Contact: ANGEL MONTERO, Md, PhD
• Phone: +34667767601
• Email: angel.monteroluis[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 106
• Est. completion date: November 1, 2021
• Est. primary completion date: September 4, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Viral

Intervention

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
• Ritonavir/lopinavir
400/100 mg/12h for 7-10 days
• Tocilizumab Injection [Actemra]
600 mg/day for 1-2 doses
• Azithromycin
500 mg/24h for 3 days
• Corticosteroid
Corticosteroids (methylprednisolone/dexamethasone/prednisone)
• Low molecular weight heparin
low molecular weight heparin (LMWH) in prophylaxis of venous thromboembolism

Device:
• Oxygen supply
Oxygen

Locations

Country	Name	City	State
Spain	Hospital Del Mar	Barcelona
Spain	Hospital Universitario Madrid Sanchinarro	Madrid
Spain	Hospital Sant Joan de Reus	Reus	Tarragona

Sponsors (4)

Lead Sponsor	Collaborator
Grupo de Investigación Clínica en Oncología Radioterapia	Hospital del Mar, Hospital Universitari Sant Joan de Reus, Hospital Universitario Madrid Sanchinarro

Country where clinical trial is conducted

Spain, 

References & Publications (10)

Arenas M, Gil F, Gironella M, Hernández V, Biete A, Piqué JM, Panés 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. Epub 2007 Nov 26. — View Citation

Arenas M, Sabater S, Hernández V, Rovirosa A, Lara PC, Biete A, Panés 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. Review. — View 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. Review. — View 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. — View 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. — View 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. Review. — View 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.

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. — View Citation

Lödermann B, Wunderlich R, Frey S, Schorn C, Stangl S, Rödel F, Keilholz L, Fietkau R, Gaipl US, Frey B. Low dose ionising radiation leads to a NF-?B dependent decreased secretion of active IL-1ß by activated macrophages with a discontinuous dose-dependency. Int J Radiat Biol. 2012 Oct;88(10):727-34. Epub 2012 May 22. — View Citation

Rödel F, Frey B, Manda K, Hildebrandt G, Hehlgans S, Keilholz L, Seegenschmiedt MH, Gaipl US, Rödel 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Day 2 after interventional radiotherapy
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Lung toxicity measured according to CTCAEv5	Day 30 and day 90 after interventional radiotherapy
Secondary	Change of the radiological image	Chest CT	Days 7 and day 30 after interventional radiotherapy
Secondary	Overall mortality	Death of any cause	Day 15 and Day 30 after interventional radiotherapy
Secondary	Measure of pro-inflammatory interleukins	Interleukins IL-6, IL-10, IL-1, IL-2, IL-8 (pg/ml)	Days 1, day 4 and day 7 after interventional radiotherapy
Secondary	Measure of trasforming growth factor (TGF-b)	TGF-ß (ng/ml)	Days 1, day 4 and day 7 after interventional radiotherapy
Secondary	Measure of tumor necrosis factor alpha (TNF-a)	TNF-a (pg/ml)	Days 1, day 4 and day 7 after interventional radiotherapy
Secondary	Determining overexpression of pro-inflammatory selectin	Overexpression of L-, E-, and P-selectin	Days 1, day 4 and day 7 after interventional radiotherapy
Secondary	Determining cell adhesion molecules (CAMs)	Overexpression of ICAM-1, VCAM	Days 1, day 4 and day 7 after interventional radiotherapy
Secondary	Measure of marker of oxidative stress PON-1	PON-1(paraoxonase and arylesterase activity) (IU/ml)	Days 1, day 4 and day 7 after interventional radiotherapy