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Low Dose Lung Radiotherapy to Treat COVID-19 Pneumonia

Primary Purpose

Covid19

Status

Completed

Phase

Not Applicable

Locations

United Kingdom

Study Type

Interventional

Intervention

Low dose Radiotherapy

About this trial

This is an interventional health services research trial for Covid19 focused on measuring SARS-CoV-2

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Lancashire Teaching Hospitals NHS

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Low Dose Radiotherapy

Arm Description

Low Dose Radiotherapy

Outcomes

Primary Outcome Measures

Feasibility of Recruitment

Feasibility to recruit to the study.

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

Secondary Outcome Measures

Withdrawal

The number of patients who withdraw from the study

Adverse events

The number of Grade 4 or higher CTCAE v5 (apart from asymptomatic lymphopenia) adverse events reported

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

Full Information

NCT ID

NCT04572412

First Posted

September 29, 2020

Last Updated

November 9, 2022

Sponsor

Lancashire Teaching Hospitals NHS Foundation Trust

Collaborators

NIHR Lancashire Clinical Research Facility

1. Study Identification

Unique Protocol Identification Number

NCT04572412

Brief Title

Low Dose Lung Radiotherapy to Treat COVID-19 Pneumonia

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Completed

Study Start Date

November 25, 2020 (Actual)

Primary Completion Date

June 30, 2022 (Actual)

Study Completion Date

June 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Lancashire Teaching Hospitals NHS Foundation Trust

Collaborators

NIHR Lancashire Clinical Research Facility

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Covid19

Keywords

SARS-CoV-2

7. Study Design

Primary Purpose

Health Services Research

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Low Dose Radiotherapy

Arm Type

Experimental

Arm Description

Low Dose Radiotherapy

Intervention Type

Radiation

Intervention Name(s)

Low dose Radiotherapy

Intervention Description

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.

Primary Outcome Measure Information:

Title

Feasibility of Recruitment

Description

Feasibility to recruit to the study.

Time Frame

6 months

Title

Tolerability of Low dose Radiotherapy

Description

Proportion of patients with no decline in PaO2/FiO2 ratio (P/F Ratio) at 48 hours after each fraction of radiotherapy

Time Frame

48 hours

Secondary Outcome Measure Information:

Title

Withdrawal

Description

The number of patients who withdraw from the study

Time Frame

6 months

Title

Adverse events

Description

The number of Grade 4 or higher CTCAE v5 (apart from asymptomatic lymphopenia) adverse events reported

Time Frame

1 month

Title

Feasibility of biochemical analysis

Description

Ability to perform lymphocyte subset, IL-6, and IL-10 analysis at baseline and 7 days post last fraction of radiotherapy

Time Frame

1 week

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dennis Hadjiyiannakis

Organizational Affiliation

LTHTR

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Aashish Vyas

Organizational Affiliation

LTHTR

Official's Role

Principal Investigator

Facility Information:

Facility Name

Lancashire Teaching Hospitals NHS

City

Preston

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

All data will be kept anonymized and confidential. Data will be held securely for 15 years pending further study.

Citations:

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

32373721

Citation

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.

Results Reference

background

PubMed Identifier

32829986

Citation

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.

Results Reference

background

Links:

URL

https://www.medrxiv.org/content/10.1101/2020.06.03.20116988v1

Description

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

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Low Dose Lung Radiotherapy to Treat COVID-19 Pneumonia

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