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

NCT04380818 | Unknown

• 1 other identifier: IPACOVID
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 3

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.

Conditions

Pneumonia, Viral

Keywords

COVID 19; RADIATION; Anti-inflammatory effects

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Day 30 and day 90 after interventional radiotherapy

• Change of the radiological image

  Days 7 and day 30 after interventional radiotherapy

• Overall mortality

  Day 15 and Day 30 after interventional radiotherapy

• Measure of pro-inflammatory interleukins

  Days 1, day 4 and day 7 after interventional radiotherapy

• Measure of trasforming growth factor (TGF-b)

  Days 1, day 4 and day 7 after interventional radiotherapy

Study Arms (2)

Control group

ACTIVE COMPARATOR

a control group only receive pharmacological treatment

Drug: Hydroxychloroquine Sulfate; Drug: Ritonavir/lopinavir; Drug: Tocilizumab Injection [Actemra]; Drug: Azithromycin; Drug: Corticosteroid; Drug: Low molecular weight heparin; Device: Oxygen supply

Experimental group

EXPERIMENTAL

an experimental group will receive low-dose lung irradiation

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

Interventions

Low-dose radiotherapy RADIATION

Bilateral low-dose lung irradiation: 0.5 Gy in a single fraction. Optionally, additional 0.5 Gy fraction 48h later

Experimental group

Hydroxychloroquine Sulfate DRUG

200 mg/12h for 5 days

Also known as: Dolquine

Control group; Experimental group

Ritonavir/lopinavir DRUG

400/100 mg/12h for 7-10 days

Also known as: Kaletra

Control group; Experimental group

Tocilizumab Injection [Actemra] DRUG

600 mg/day for 1-2 doses

Also known as: Actemra

Control group; Experimental group

Azithromycin DRUG

500 mg/24h for 3 days

Control group; Experimental group

Corticosteroid DRUG

Corticosteroids (methylprednisolone/dexamethasone/prednisone)

Control group; Experimental group

Low molecular weight heparin DRUG

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

Control group; Experimental group

Oxygen supply DEVICE

Oxygen

Control group; Experimental group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Age \<18 years
• Leukopenia \<1000
• Pregnancy
• Not understanding or refusing the purpose of the study

Sponsors & Collaborators

• Grupo de Investigación Clínica en Oncología Radioterapia: lead
• Hospital Universitario Madrid Sanchinarro: collaborator
• Hospital del Mar: collaborator
• Hospital Universitari Sant Joan de Reus: collaborator

Study Sites (3)

Hospital Sant Joan de Reus

Reus, Tarragona, 43204, Spain

NOT YET RECRUITING

Hospital Del Mar

Barcelona, 08003, Spain

NOT YET RECRUITING

Hospital Universitario Madrid Sanchinarro

Madrid, 28050, Spain

RECRUITING

Related Publications (11)

• 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.

  PMID: 32171193 BACKGROUND

• 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.

  PMID: 23057008 BACKGROUND

• 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.

  PMID: 22907572 BACKGROUND

• 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.

  PMID: 18031855 BACKGROUND

• 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.

  PMID: 22545750 BACKGROUND

• 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.

  PMID: 24348219 BACKGROUND

• 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.

  PMID: 31060383 BACKGROUND

• 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.

  PMID: 32342871 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 32437820 BACKGROUND

• 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.

  PMID: 32613089 DERIVED

MeSH Terms

Conditions

Pneumonia, Viral; COVID-19

Interventions

Radiotherapy; Hydroxychloroquine; lopinavir-ritonavir drug combination; tocilizumab; Azithromycin; Adrenal Cortex Hormones; Heparin, Low-Molecular-Weight

Condition Hierarchy (Ancestors)

Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Lung Diseases; Respiratory Tract Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Therapeutics; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ANGEL MONTERO, Md, PhD

CONTACT

+34667767601; angel.monteroluis@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2020
• First Posted: May 8, 2020
• Study Start: June 5, 2020
• Primary Completion: September 4, 2021
• Study Completion: November 1, 2021
• Last Updated: July 30, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Protocol/ICF from approval Individual epidemiological and clinical data after recruitment is complete.

Locations

ES (3)