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

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ClinicalTrials.gov Identifier: NCT04904783
Recruitment Status : Recruiting
First Posted : May 27, 2021
Last Update Posted : June 15, 2021
Sponsor:
Information provided by (Responsible Party):
Niloy Ranjan Datta, Mahatma Gandhi Institute of Medical Sciences

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.

Condition or disease Intervention/treatment Phase
COVID-19 Pneumonia Radiation: Low dose radiotherapy Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Low-Dose Radiation Therapy in COVID-19
Actual Study Start Date : June 1, 2021
Estimated Primary Completion Date : July 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Active Comparator: Study arm
10 patients of confirmed diagnosis of moderate COVID-19 who fulfil the inclusion criteria and give written informed consent would be in study arm. All patients, belong to both study and control groups would receive the same treatment (oxygen support, steroids, anticoagulant therapy, remdesivir and other supportive therapy) as per the Institute guidelines for management of moderate COVID-19 disease. Only low dose radiotherapy would be added to patients in the study arm.
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.

No Intervention: Control Arm
10 patients of confirmed diagnosis of moderate COVID-19 who fulfil the inclusion criteria and have not given written informed consent would be in study arm. These patients would receive the same treatment (oxygen support, steroids, anticoagulant therapy, remdesivir and other supportive therapy) as per the Institute guidelines for management of moderate COVID-19 disease except low dose radiotherapy.



Primary Outcome Measures :
  1. Number of patients dying due to COVID-19 [ Time Frame: 28 days from the date of diagnosis ]
    Compare the number of patients whose death could be ascribed to COVID-19 in the two groups

  2. Mean duration of hospital stay for surviving patients [ Time Frame: 28 days from the date of diagnosis / discharge ]
    Compare the mean duration of hospital stay between the patients surviving in study and control groups


Secondary Outcome Measures :
  1. Mean dose of steroid requirement for surviving patients [ Time Frame: 28 days from the date of diagnosis ]
    Compare the mean total dose of steroid required in between the patients surviving in study and control groups

  2. Mean time to completely wean off from Oxygen (02) supplementation for surviving patients [ Time Frame: 28 days from the date of diagnosis / discharge ]
    Compare the mean time to completely wean off from Oxygen supplementation in patients between the patients surviving in study and control groups

  3. Changes in the biochemical profiles of Interleukin-6 (IL-6) [ Time Frame: 28 days from the date of diagnosis / discharge ]
    IL-6 levels in control vs study group patients

  4. Changes in the biochemical profiles of quantitative C reactive protein (CRP) [ Time Frame: 28 days from the date of diagnosis / discharge ]
    Quantitative CRP levels in control vs study group patients

  5. Changes in the biochemical profiles of D-Dimer [ Time Frame: 28 days from the date of diagnosis / discharge ]
    D-Dimer levels in control vs study group patients

  6. Changes in the biochemical profiles of Ferritin [ Time Frame: 28 days from the date of diagnosis / discharge ]
    Ferritin levels in control vs study group patients

  7. Acute pulmonary toxicities that may be attributable to LDRT [ Time Frame: 28 days from the date of diagnosis / discharge ]
    Acute pulmonary toxicities as per the Common Terminology Criteria for Adverse Events (CTCAE) version 5

  8. Total cost of hospital stay following LDRT for surviving patients [ Time Frame: 28 days from the date of diagnosis / discharge ]
    Cost evaluation and comparison between the patients surviving in study and control groups



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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04904783


Contacts
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Contact: Niloy R Datta, MD,DNB +91- 9717388117 niloydatta@mgims.ac.in
Contact: Jyoti Jain, MD, PhD +91-9850517839 jyotijain@mgims.ac.in

Locations
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India
Mahatma Gandhi Institute of Medical Sciences, Recruiting
Sevagram, Maharashtra, India, 442102
Contact: Niloy R Datta, MD, DNB    +919717388117    niloydatta@magims.ac.in   
Contact: Jyoti Jain, MD, PhD    +919850517839    jyotijain@mgims.ac.in   
Mahatma Gandhi Institute of Medical Sciences Recruiting
Sevagram, Maharashtra, India, 442102
Contact: Niloy R Datta, MD, DNB    +919717388117    niloydatta@magims.ac.in   
Contact: Jyoti Jain, MD, PhD    +919850517839    jyotijain@mgims.ac.in   
Sponsors and Collaborators
Mahatma Gandhi Institute of Medical Sciences
Investigators
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Principal Investigator: Niloy R Datta, MD,DNB Dept of Radiotherapy, Mahatma Gandhi Institute of Medical Sciences, India
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Responsible Party: Niloy Ranjan Datta, Director-Professor & Head, Department of Radiotherapy, Mahatma Gandhi Institute of Medical Sciences
ClinicalTrials.gov Identifier: NCT04904783    
Other Study ID Numbers: MGIMS/IEC/RADTHP/215/2021
First Posted: May 27, 2021    Key Record Dates
Last Update Posted: June 15, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Not yet decided. Will decide later after the study results are available
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: 6 months from date of publication of the final results.
Access Criteria: On request to Principal investigator

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Niloy Ranjan Datta, Mahatma Gandhi Institute of Medical Sciences:
COVID-19
Pneumonia
Low dose radiotherapy
Cytokine storm
Additional relevant MeSH terms:
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Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections