Clinical trial NCT04904783: Low-Dose Radiation Therapy to Lungs in Moderate COVID-19 Pneumonitis: A Case-Control Pilot Study
Official title: Low-Dose Radiation Therapy in COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: COVID-19
Pneumonia
Keywords: COVID-19
Pneumonia
Low dose radiotherapy
Cytokine storm
Lead sponsor: Mahatma Gandhi Institute of Medical Sciences
Sponsor class: OTHER
First posted: 2021-05-27
Enrollment: 20
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: To explore the role of low dose pulmonary radiotherapy (LDRT) in moderate disease category of COVID-19 patients with pneumonitis in terms of the following primary and secondary objectives. The outcome of LDRT in a pilot group of 10 patients (Study group) would be compared with another 10 patients (Control group) who have not given consent for LDRT and/or would not able to be able to lie down still for the entire treatment duration in the radiotherapy unit. This is not a randomized but a case-control study.
Primary purpose: TREATMENT

Brief summary: This pilot case-control study at Mahatma Gandhi Institute of Medical Sciences (MGIMS), Sevagram, India is designed to evaluate the use of low dose radiotherapy (LDRT) in patients with moderate COVID-19 with specific objectives to abrogate the onset of cytokine storm and thus facilitate their early recovery and reduce mortality.

Detailed description: One of the primary attributes to the mortality in coronavirus disease -19 (COVID-19) is acute respiratory distress syndrome (ARDS) induced by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) mediated cytokine storm (CS).To mitigate the ARDS, an ideal approach would be to diminish the viral load by activating immune cells for CS prevention or to suppress the overactive cytokine-releasing immune cells. The search for ideal pharmaceutical agent/s to take care of SARS-CoV-2 mediated CS is still eluding the clinicians. The only drugs with modest clinical benefit are remdesivir and dexamethasone. The availability of the former is uncertain while an overdependence on steroids could prove counterproductive as evident from increasing incidence of fatal mucormycosis reported in post-COVID patients treated with steroids. The situation for COVID-19 patients successfully treated with steroids is akin to "from frying pan into the fire".

Thus, concerted efforts are needed to prevent the onset of CS in COVID-19. This, would directly help to lower the mortality. One of the approaches being recently investigated worldwide, is the use of single low dose radiotherapy (LDRT) of 0.5 - 1.5 Gy to the lungs before the onset of CS in moderately affected COVID-19 patients requiring oxygen supplementation. This crucial window of opportunity needs to be exploited with LDRT to mitigate the onset of the fatal CS.

LDRT could thus be a potential game changer in the management of COVID-19. LDRT with its multipronged actions may attenuate immune activation and consequently mitigate the production of pro-inflammatory cytokines. A number of centers have reported encouraging outcomes in pilot studies with LDRT. There has been a significant reduction in oxygen requirement within just 72 hours of LDRT, resulting in reduced hospital stay and deaths. This pilot case-control study at MGIMS is designed to evaluate the use of LDRT in patients with moderate COVID-19 with specific objectives to prevent the onset of CS and thus facilitate their early recovery and reduce mortality.

Eligibility criteria: Inclusion Criteria:

* Reverse transcription polymerase chain reaction (RT-PCR) / Rapid Ag test positive
* Signed informed consent
* Age ≥ 50 yrs
* Respiratory rate : 25 - 30/min, breathless AND/OR
* Oxygen saturation by pulse oximetry (SpO2) in 90 - 93% on room air (readings taken after 5 mins of stopping oxygen supplementation)
* Rising levels of quantitative-CRP and/or D-Dimer and/or Ferritin in 2 consecutive samples taken 24 hours apart

Exclusion Criteria:

* Patient who have received vaccination for COVID-19 (single / both doses of any approved vaccine)
* Hemodynamic instability in shock and/or systolic BP \< 90mm Hg
* Septicemia
* Disseminated intravascular coagulation
* Requiring ventilation
* Unable to lie down supine
* Severe acute respiratory distress with Fraction of inspired oxygen (FiO2) \< 100mm Hg
* Cardiac defibrillator/pacemaker in situ
* Lymphocyte count \< 1 x 106/ml
* Pregnancy and/or lactating mothers
* HIV and/or HbsAg positive patients

Primary outcomes:
measure: Number of patients dying due to COVID-19
timeFrame: 28 days from the date of diagnosis
measure: Mean duration of hospital stay for surviving patients
timeFrame: 28 days from the date of diagnosis / discharge
Secondary outcomes:
measure: Mean dose of steroid requirement for surviving patients
timeFrame: 28 days from the date of diagnosis
measure: Mean time to completely wean off from Oxygen (02) supplementation for surviving patients
timeFrame: 28 days from the date of diagnosis / discharge
measure: Changes in the biochemical profiles of Interleukin-6 (IL-6)
timeFrame: 28 days from the date of diagnosis / discharge
measure: Changes in the biochemical profiles of quantitative C reactive protein (CRP)
timeFrame: 28 days from the date of diagnosis / discharge
measure: Changes in the biochemical profiles of D-Dimer
timeFrame: 28 days from the date of diagnosis / discharge
measure: Changes in the biochemical profiles of Ferritin
timeFrame: 28 days from the date of diagnosis / discharge
measure: Acute pulmonary toxicities that may be attributable to LDRT
timeFrame: 28 days from the date of diagnosis / discharge
measure: Total cost of hospital stay following LDRT for surviving patients
timeFrame: 28 days from the date of diagnosis / discharge
Other outcomes:
Locations:
city: Sevagram
country: India
facility: Mahatma Gandhi Institute of Medical Sciences,
state: Maharashtra
city: Sevagram
country: India
facility: Mahatma Gandhi Institute of Medical Sciences
state: Maharashtra
Study officials:
affiliation: Dept of Radiotherapy, Mahatma Gandhi Institute of Medical Sciences, India
name: Niloy R Datta, MD,DNB
role: PRINCIPAL_INVESTIGATOR
References: