Low Dose Lung Radiotherapy to Treat COVID-19 Pneumonia

Low Dose Lung Radiotherapy to Treat COVID-19 Pneumonia (a Phase I Feasibility Trial)

The purpose of this study is to document the feasibility and tolerability of low dose thoracic radiotherapy in patients with WHO level 5 COVID 19 infections.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Radiation: Low dose Radiotherapy

Detailed Description

Subjects will be identified following admission to hospital who test positive for COVID-19 infection. They will then be informed and consented, and eligibility confirmed and registered to study. Following this the first, sentinel patient, will be treated with 0.5Gy dose radiotherapy to cover the lungs, with heterogeneity correction. A further 0.5Gy dose can be repeated within 96 hours. There shall then be a 7 day gap prior to recruiting patient 2. The remaining patients will be recruited, treated and observed in cohorts of 3.

The patients shall then be followed up at 48 hours post Radiotherapy, 7 days post radiotherapy and 29 days post radiotherapy. With assessment of Physiological parameters, survival status, laboratory testing and imaging performed on follow up at 7 and 29 days.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Preston, United Kingdom
    • Lancashire Teaching Hospitals NHS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 50 years.
• Patients have symptoms of COVID-19 infection as per WHO guidelines (e.g. cough, fever, dyspnea, etc.) for under 5 days from hospital admission.
• Patients are hospitalized and meet the criteria for WHO level 5 COVID pneumonia. In addition:
• SpO2 <94% on Room Air;
• Respiratory rate >20 Breaths per minute on Room Air.
• Laboratory confirmed COVID-19 infection based on PCR.
• Patients need ward-based oxygen between 28 to 40%.
• Patients able to provide witnessed verbal informed consent.
• Patient is free of other severe medical conditions that would preclude radiotherapy treatment (e.g. severe recent CVA).

Exclusion Criteria:

• Pregnant or lactating women.
• Presence of secondary infection with procalcitonin assessment at baseline.
• Patient is generating aerosols e.g. use of CPAP device.
• Hereditary syndromes known to have increase sensitivity to Radiotherapy including, but not limited to, ataxia-telangiectasia, and Njemgen Breakage Syndrome.
• History of prior thoracic radiotherapy.
• Inability to undergo radiotherapy for any reason as determined by the treating medical team.
• Alternative diagnosis for lung compromise unrelated to COVID-19 / deemed more likely than COVID-19 related lung compromise.
• Inability to consent directly.
• If patient has participated in any other COVID-19 therapy study within the last month (4 weeks).
• Pre-existing generalized pulmonary fibrosis.
• Known prior systemic use of the following drugs within the last 6 months: Bleomycin, Carmustine, Methotrexate, Busulfan, Cyclophosphamide, or Amiodarone.
• History of lung lobectomy or pneumonectomy.
• Known history of pulmonary sarcoidosis, Wegener's Granulomatosis, Systemic Lupus Erythematosus, or other autoimmune disease affecting lungs.
• Symptomatic congestive heart failure within the past 6 months including during hospitalization.
• History of recent or current malignancy receiving any cytotoxic chemotherapy or immunotherapy within the past 6 months.
• Bone marrow transplantation.
• Latent tuberculosis.
• Any solid organ transplant (renal, cardiac, liver, lung) requiring immunosuppressive therapy.
• Septic shock and organ dysfunction.
• Severe ARDS P/F ratio ≤100mmHg.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: HEALTH_SERVICES_RESEARCH
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Low Dose Radiotherapy

Radiation: Low dose Radiotherapy; External Beam irradiation, single fraction of 0.5Gy, to be delivered within 48 hours of enrolment to study. With field to cover as close to lung edges as AP/PA technique allows. A further 0.5GY to the thorax given up to 96 hours apart from first fraction is permitted, if a patient had either (a) responded to the first dose but then deteriorated, however remaining better than baseline level or (b) stabilized after first dose but not fully improved.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Recruitment	Feasibility to recruit to the study.	6 months
Tolerability of Low dose Radiotherapy	Proportion of patients with no decline in PaO2/FiO2 ratio (P/F Ratio) at 48 hours after each fraction of radiotherapy	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Withdrawal	The number of patients who withdraw from the study	6 months
Adverse events	The number of Grade 4 or higher CTCAE v5 (apart from asymptomatic lymphopenia) adverse events reported	1 month
Feasibility of biochemical analysis	Ability to perform lymphocyte subset, IL-6, and IL-10 analysis at baseline and 7 days post last fraction of radiotherapy	1 week

Collaborators and Investigators

• Sponsor: Lancashire Teaching Hospitals NHS Foundation Trust
• Collaborators: NIHR Lancashire Clinical Research Facility
• Investigators: Principal Investigator: Dennis Hadjiyiannakis, LTHTR; Principal Investigator: Aashish Vyas, LTHTR

Publications and helpful links

General Publications

• Lara PC, Burgos J, Macias D. Low dose lung radiotherapy for COVID-19 pneumonia. The rationale for a cost-effective anti-inflammatory treatment. Clin Transl Radiat Oncol. 2020 Apr 25;23:27-29. doi: 10.1016/j.ctro.2020.04.006. eCollection 2020 Jul.
• 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.
• Hadjiyiannakis D, Dimitroyannis D, Eastlake L, Peedell C, Tripathi L, Simcock R, Vyas A, Deutsch E, Chalmers AJ. Personal View: Low-Dose Lung Radiotherapy Should be Evaluated as a Treatment for Severe COVID-19 Lung Disease. Clin Oncol (R Coll Radiol). 2021 Jan;33(1):e64-e68. doi: 10.1016/j.clon.2020.08.003. Epub 2020 Aug 14. No abstract available.

Helpful Links

• Low-Dose Whole-Lung Radiation for COVID-19 Pneumonia: Planned Day-7 Interim Analysis of a Registered Clinical Trial

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 25, 2020
• Primary Completion (ACTUAL): June 30, 2022
• Study Completion (ACTUAL): June 30, 2022

Study Registration Dates

• First Submitted: September 29, 2020
• First Submitted That Met QC Criteria: September 30, 2020
• First Posted (ACTUAL): October 1, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 10, 2022
• Last Update Submitted That Met QC Criteria: November 9, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia
• Other Study ID Numbers: 285167

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All data will be kept anonymized and confidential. Data will be held securely for 15 years pending further study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No