Clinical trial NCT04390412: Low Dose Radiotherapy in COVID-19 Pneumonia
Official title: Assessment of Adding Low Dose Pulmonary Radiotherapy to the National Protocol of COVID-19 Management: A Pilot Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: COVID
SARS (Severe Acute Respiratory Syndrome)
Keywords: Low Dose Lung Radiotherapy
COVID-19
anti-inflammatory
Lead sponsor: Shahid Beheshti University of Medical Sciences
Sponsor class: OTHER
First posted: 2020-05-15
Enrollment: 5
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: Moderate to severe cases of SARS-associated ARDS based on inclusion/ exclusion criteria and the decision made in multi- disciplinary team are treated with 0.5 Gy whole lung radiation.

Detailed description: SARS-associated ARDS (acute respiratory distress syndrome) is the most fatal outcome of COVID-19 systemic infection. To overcome the uncontrolled inflammation leading to ARDS and respiratory failure, several drugs have been investigated in this situation with the most promising results coming from anti-inflammatory agents that directly or indirectly inhibit IL-6 and its counterparts of inflammation.

Low dose radiation, as opposed to high dose, has documented anti-inflammatory effects that are exercised through various mechanisms including decrease in pro-inflammatory cytokines such as IL-6.

In this pilot clinical trial, the patients are carefully selected according to inclusion /exclusion criteria and the clinical judgement of the multi- disciplinary team.Their diagnostic CT scan will be used to plan an AP/ PA radiotherapy treatment to both lungs and the set-up positioning information is obtained from anatomical landmarks. The patient will be referred for a fraction of 0.5 Gy to both lungs and for the next 28 days the clinical para-clinical and radiologic variables of disease severity will be monitored closely. Should the patient's clinical course indicate and the multi- disciplinary team approves, they may be subjected to another fraction of 0.5 Gy to a maximum of 1 Gy in two fractions at least 72 hours apart. All the patients will also receive the standard national protocol of COVID-19 management.

A total of 5 patients will be enrolled in the RT arm, providing favourable results seen in the first set of patients, the team will decide on recruiting a larger number for a phase II clinical trial.

Eligibility criteria: Inclusion Criteria:

* Confirmed COVID-19 diagnosis ( PCR or serologic or radiographic)
* Presence of pulmonary involvement ( defined by P/F ratio or NIV need)
* Less than 3 days since the onset of ARDS
* Age \> 60 years
* ↑ IL-6 ( if available)
* ↑ CRP

Exclusion Criteria:

* Lack of informed consent
* Inability to transfer to the radiation unit
* Hemodynamic instability
* Septic shock and organ dysfunction
* Severe ARDS P/F ratio ≤ 100 mmHg
* History of cardiac failure
* Contraindications to radiation

Primary outcomes:
measure: Change from baseline blood oxygenation
timeFrame: 28 days
measure: Number of Hospital stay days
timeFrame: 28 days
measure: Number of ICU stay days
timeFrame: 28 days
measure: Number of intubation events
timeFrame: 28 days
Secondary outcomes:
measure: WBC
timeFrame: 28 days
measure: Platelets
timeFrame: 28 days
measure: CRP
timeFrame: Day 1
measure: CRP
timeFrame: Day 2
measure: CRP
timeFrame: Day 3
measure: CRP
timeFrame: Day 4
measure: CRP
timeFrame: Day 5
measure: IL-6
timeFrame: Day 1
measure: IL-6
timeFrame: Day 2
measure: IL-6
timeFrame: Day 3
measure: IL-6
timeFrame: Day 4
measure: IL-6
timeFrame: Day 5
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Imam Hossein Hospital
Study officials:
affiliation: Shahid Beheshti University of Medical Sciences
name: Ahmad Ameri, Prof.
role: STUDY_CHAIR
affiliation: Shahid Beheshti University of Medical Sciences
name: Nazanin Rahnama, M.D.
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: Large M, Hehlgans S, Reichert S, Gaipl US, Fournier C, Rodel C, Weiss C, Rodel F. Study of the anti-inflammatory effects of low-dose radiation: The contribution of biphasic regulation of the antioxidative system in endothelial cells. Strahlenther Onkol. 2015 Sep;191(9):742-9. doi: 10.1007/s00066-015-0848-9. Epub 2015 Jun 8.
citation: Clayton B. Hess, MD, MPH, and Mohammad K. Khan, MD, PhD, "Low dose chest radiation for COVID-19 patients" Winship Emory News post, April 27, 2020
citation: 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.
citation: Kefayat A, Ghahremani F. Low dose radiation therapy for COVID-19 pneumonia: A double-edged sword. Radiother Oncol. 2020 Jun;147:224-225. doi: 10.1016/j.radonc.2020.04.026. Epub 2020 Apr 20. No abstract available.
citation: Stefano M Magrini, Prof et al. COVID-19 Pneumonitis Low Dose Lung Radiotherapy (COLOR-19). ClinicalTrials.gov Identifier: NCT04377477