Low-Dose Radiation Therapy to Lungs in Moderate COVID-19 Pneumonitis: A Case-Control Pilot Study

COVID-19 Clinical Trial

— LOCORAD  

Official title:

Low-Dose Radiation Therapy in COVID-19

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04904783
• Other study ID #: MGIMS/IEC/RADTHP/215/2021
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2021
• Est. completion date: December 31, 2021

Study information

• Verified date: July 2021
• Source: Mahatma Gandhi Institute of Medical Sciences
• Contact: Niloy R Datta, MD,DNB
• Phone: +91- 9717388117
• Email: niloydatta[@]mgims.ac.in
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Pneumonia

Intervention

Radiation:
• Low dose radiotherapy
Patients in study group will receive LDRT to both lungs by two parallel opposed fields, antero-posterior (AP) and postero-anterior (PA) to deliver a midplane dose of 0.5 Gy in a single fraction. As this dose is very less, doses to the critical structures including heart and lungs would be very low. All the patients will be treated on Telecobalt unit (Theratronics Phoenix, Canada) and not on the linear accelerator to avoid risks to cancer patients on treatment with linear accelerator. CT based plan will not be undertaken for logistic issues and is also not felt to be mandatory for this LDRT. Dose computation would be carried out by manual dose calculation for the Telecobalt unit.

Locations

Country	Name	City	State
India	Mahatma Gandhi Institute of Medical Sciences	Sevagram	Maharashtra
India	Mahatma Gandhi Institute of Medical Sciences,	Sevagram	Maharashtra

Sponsors (1)

Lead Sponsor	Collaborator
Mahatma Gandhi Institute of Medical Sciences

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients dying due to COVID-19	Compare the number of patients whose death could be ascribed to COVID-19 in the two groups	28 days from the date of diagnosis
Primary	Mean duration of hospital stay for surviving patients	Compare the mean duration of hospital stay between the patients surviving in study and control groups	28 days from the date of diagnosis / discharge
Secondary	Mean dose of steroid requirement for surviving patients	Compare the mean total dose of steroid required in between the patients surviving in study and control groups	28 days from the date of diagnosis
Secondary	Mean time to completely wean off from Oxygen (02) supplementation for surviving patients	Compare the mean time to completely wean off from Oxygen supplementation in patients between the patients surviving in study and control groups	28 days from the date of diagnosis / discharge
Secondary	Changes in the biochemical profiles of Interleukin-6 (IL-6)	IL-6 levels in control vs study group patients	28 days from the date of diagnosis / discharge
Secondary	Changes in the biochemical profiles of quantitative C reactive protein (CRP)	Quantitative CRP levels in control vs study group patients	28 days from the date of diagnosis / discharge
Secondary	Changes in the biochemical profiles of D-Dimer	D-Dimer levels in control vs study group patients	28 days from the date of diagnosis / discharge
Secondary	Changes in the biochemical profiles of Ferritin	Ferritin levels in control vs study group patients	28 days from the date of diagnosis / discharge
Secondary	Acute pulmonary toxicities that may be attributable to LDRT	Acute pulmonary toxicities as per the Common Terminology Criteria for Adverse Events (CTCAE) version 5	28 days from the date of diagnosis / discharge
Secondary	Total cost of hospital stay following LDRT for surviving patients	Cost evaluation and comparison between the patients surviving in study and control groups	28 days from the date of diagnosis / discharge