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Low Dose Whole Lung Radiation Therapy for Patients With COVID-19 and Respiratory Compromise (VENTED)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04427566
Recruitment Status : Recruiting
First Posted : June 11, 2020
Last Update Posted : March 15, 2021
Sponsor:
Information provided by (Responsible Party):
Arnab Chakravarti, Ohio State University Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE June 5, 2020
First Posted Date  ICMJE June 11, 2020
Last Update Posted Date March 15, 2021
Actual Study Start Date  ICMJE July 23, 2020
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 9, 2020)
Mortality rate of subjects treated with whole lung low-dose radiation [ Time Frame: up to 28 days post radiation delivery ]
Death date of subjects will be collected from the date of radiation up to 1 month post radiation dose
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2020)
  • Survival rate of subjects treated with whole lung low-dose radiation [ Time Frame: up to 18 months post radiation delivery ]
    Subject survival will be collected in number of days through 18 months post treatment
  • Change in number of Intensive care unit days [ Time Frame: up to 28 days post radiation delivery ]
    Number of intensive care days
  • Change in number of days using supplemental oxygen [ Time Frame: up to 28 days post radiation delivery ]
    Number of days using supplemental oxygen
  • Change in oxygenation index/oxygen saturation index for 14 days post treatment or until extubated [ Time Frame: up to 28 days post radiation ]
    Oxygenation index/oxygen saturation until extubation
  • Quantitation of Lung Involvement using Chest CT [ Time Frame: up to 28 days post radiation ]
    Measure as a percent, the amount of pneumonia involvement of each lung segment (right upper lobe, right middle lobe, right lower lobe, left upper lobe and left lower lobe) from chest CT images at day 7, 14 and 28. Each lung segment can have involvement from 0 % (no involvement) up to 100% (complete pneumonia involvement of segment)
  • Quantitation of Lung Opacities using Chest CT [ Time Frame: up to 28 days post radiation ]
    Semi-quantitation of ground glass opacities or lung opacification with a score of 0-5 from Chest CT images at day 7, 14 and 28 for each of the 5 lobes of the lungs. The scoring system is as follows: 0, no involvement; 1, <5% involvement; 2, 25% involvement, 3, 26-49% involvement; 4, 50-75% involvement; and 5, >75% involvement.
  • SARS-CoV2 viral titers [ Time Frame: up to 28 days ]
    Determine viral titers at baseline, days 7, 14 and 28.
  • Incidence of adverse events, including severity and duration, for administration of low dose radiation to lungs [ Time Frame: up to 28 days ]
    Review adverse events, including severity and duration, for all subjects to determine safety of the radiation treatment for pneumonia due to COVID-19.
  • Change in performance status after low dose radiation to lungs [ Time Frame: up to 28 days ]
    Performance status will be evaluated using the Karnofsky Performance Scale Index at baseline, 7, 14 and 28 days post radiation dose. Scores range from 100 (normal, no complaints) to 0 (dead). A higher number indicates the ability to carry out normal daily activities.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2020)
  • Survival rate of subjects treated with whole lung low-dose radiation [ Time Frame: up to 18 months post radiation delivery ]
    Subject survival will be collected in number of days through 18 months post treatment
  • Change in number of Intensive care unit days [ Time Frame: up to 28 days post radiation delivery ]
    Number of intensive care days
  • Change in number of days using supplemental oxygen [ Time Frame: up to 28 days post radiation delivery ]
    Number of days using supplemental oxygen
  • Change in oxygenation index/oxygen saturation index for 14 days post treatment or until extubated [ Time Frame: up to 28 days post radiation ]
    Oxygenation index/oxygen saturation until extubation
  • Quantitation of Lung Involvement using Chest CT [ Time Frame: up to 28 days post radiation ]
    Measure as a percent, the amount of pneumonia involvement of each lung segment (right upper lobe, right middle lobe, right lower lobe, left upper lobe and left lower lobe) from chest CT images at day 7, 14 and 28. Each lung segment can have involvement from 0 % (no involvement) up to 100% (complete pneumonia involvement of segment)
  • Quantitation of Lung Opacities using Chest CT [ Time Frame: up to 28 days post radiation ]
    Measure the size of ground glass opacities or lung opacification in cm from Chest CT images at day 7, 14 and 28.
  • SARS-CoV2 viral titers [ Time Frame: up to 28 days ]
    Determine viral titers at baseline, days 7, 14 and 28.
  • Safety of administration of low dose radiation to lungs [ Time Frame: up to 28 days ]
    Review adverse events, including severity and duration, for all subjects to determine safety of the radiation treatment for pneumonia due to COVID-19.
  • Change in performance status after low dose radiation to lungs [ Time Frame: up to 28 days ]
    Performance status will be evaluated using the Karnofsky Performance Scale Index at baseline, 7, 14 and 28 days post radiation dose. Scores range from 100 (normal, no complaints) to 0 (dead). A higher number indicates the ability to carry out normal daily activities.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Low Dose Whole Lung Radiation Therapy for Patients With COVID-19 and Respiratory Compromise
Official Title  ICMJE Vented COVID: A Phase II Study Of The Use Of Ultra Low-Dose Bilateral Whole Lung Radiation Therapy in the Treatment Of Critically Ill Patients With COVID-19 Respiratory Compromise
Brief Summary

Low doses of radiation in the form of chest X-rays have been used to treat people with pneumonia. This treatment was found to be effective by reducing inflammation and with minimal side effects. However, it was an expensive treatment and was eventually replaced with less costly treatments such as antibiotics. Radiation has also been shown in some animal experiments to reduce some types of inflammation.

Some patients diagnosed with COVID-19 pneumonia will experience worsening disease, which can become very serious, requiring the use of a ventilator. This is caused by inflammation in the lung from the virus and the immune system. For this study, the x-ray given is called radiation therapy. Radiation therapy uses high-energy X-ray beams from a large machine to target the lungs and reduce inflammation. Usually, it is given at much higher doses to treat cancers.

The purpose of this study is to find out if adding a single treatment of low-dose x-rays to the lungs might reduce the amount of inflammation in the lungs from a COVID-19 infection, which could help a patient to breathe without use of a ventilator.

Detailed Description

The primary outcome is the mortality rate 30 days after the ICU-based mechanical ventilation initiation.Based on current data available, the mortality rate for ventilated patients is assumed to be 80% in the current design. An interim futility analysis will be conducted after 16 evaluable patients have received the ultralow dose-whole lung radiation therapy (ULD-WLRT). If at least 3 patients survive for at least 30 days, we will enroll additional 8 patients (total of 24 patients). Otherwise, the trial will stop for further evaluation. Due to the limited data currently available in local institutions about a 30 day mortality rate , we will retrospectively evaluate the mortality rate of the ventilated patients without the ULD-WLRT in our institution when data is available.

Time to event secondary objectives (e.g. overall survival, time to discharge) analyses will be performed using Kaplan-Meier survival analysis, with a competing risk model (leaving the study because of death), including effects for demographic/clinical characteristics in the model. Proportional endpoints (such as % patients off ventilator) will be calculated along with the 95% Clopper-Pearson exact confidence interval. Pre/post measurements will be evaluated using linear mixed models for repeated measures (with proper data transformation as needed). Association between demographic/clinical characteristics and other secondary objectives (size of ground glass opacities (GGO)/opacification, for example) will be accomplished with generalized linear models.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE Radiation: Radiation therapy
Patients will be treated with a single dose of 80 cGy to the bilateral lungs in a manner that is simplified such that it can be designed and delivered quickly in one session. No specific normal tissue constraints are employed in this protocol.
Other Names:
  • Linear accelerator
  • x-rays
  • LINAC
Study Arms  ICMJE Experimental: Radiation Arm
Each subject will receive a dose of whole lung radiation. A second optional dose of 80 cGy may be delivered if no improvement after 3-10 days.
Intervention: Radiation: Radiation therapy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 9, 2020)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Laboratory Diagnosis of COVID-19 based within 14 days of enrollment.
  • CT or radiographic findings typical of COVID-19 pneumonia within 5 days of enrollment
  • Receiving ICU-based mechanical ventilation
  • Life expectancy ≥ 24 hours, as judged by investigator
  • Hypoxemia defined as a Pa/FIO2 ratio < 300 or SpO2/FiO2 < 315
  • Signed informed consent by patient or his or her legal/authorized representative

Exclusion Criteria:

  • Moribund with survival expected < 24 hours, as judged by investigator and treating team
  • Expected survival < 30 days, as judged by investigator and treating team, due to chronic illness present prior to COVID infection
  • Patient or legal representative not committed to full disease specific therapy, i.e. comfort care (DNRCCA is allowed)
  • Treatment with immune suppressing medications in the last 30 days (steroids for acute respiratory distress syndrome or septic shock allowed)
  • Presumed COVID-associated illness greater than 14-days
  • Inpatient admission greater than 14-days
  • Patient deemed unsafe for travel for radiation therapy
  • Chronic hypoxemia requiring supplemental oxygen at baseline
  • Documented active connective tissue disease (scleroderma) or idiopathic pulmonary fibrosis
  • History of prior radiation therapy resulting in ≥grade 2 radiation pneumonitis within 365 days of enrollment
  • Active or history of prior radiation to the thorax completed within 180 days of enrollment (skin or surface only skin treatments are acceptable)
  • Known active uncontrolled bacterial or fungal infections of the lung.
  • Active cytotoxic chemotherapy
  • Females who are pregnant or have a positive pregnancy test
  • Breast feeding
  • Note: concurrent administration of convalescent immune plasma therapy either on clinical trial or as a standard therapy not an exclusion criterion, but will be noted
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Arnab Chakravarti 614-293-0672 Arnab.Chakravarti@osumc.edu
Contact: Kimberly Mahler 614-685-4247 kimberly.mahler@osumc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04427566
Other Study ID Numbers  ICMJE VENTED
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Arnab Chakravarti, Ohio State University Comprehensive Cancer Center
Study Sponsor  ICMJE Ohio State University Comprehensive Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Arnab Chakravarti James Cancer Hospital, Department of Radiation Oncology
PRS Account Ohio State University Comprehensive Cancer Center
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP