Clinical trial NCT04572412: 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
Overall status: COMPLETED
Phase: NA
Conditions: Covid19
Keywords: SARS-CoV-2
Lead sponsor: Lancashire Teaching Hospitals NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: NIHR Lancashire Clinical Research Facility
First posted: 2020-10-01
Enrollment: 2
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: HEALTH_SERVICES_RESEARCH

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.

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.

Primary outcomes:
measure: Feasibility of Recruitment
timeFrame: 6 months
measure: Tolerability of Low dose Radiotherapy
timeFrame: 48 hours
Secondary outcomes:
measure: Withdrawal
timeFrame: 6 months
measure: Adverse events
timeFrame: 1 month
measure: Feasibility of biochemical analysis
timeFrame: 1 week
Other outcomes:
Locations:
city: Preston
country: United Kingdom
facility: Lancashire Teaching Hospitals NHS
Study officials:
affiliation: LTHTR
name: Dennis Hadjiyiannakis
role: PRINCIPAL_INVESTIGATOR
affiliation: LTHTR
name: Aashish Vyas
role: PRINCIPAL_INVESTIGATOR
References:
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: 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.
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.