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

Primary Purpose

COVID-19

Status

Unknown status

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Radiation therapy

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring ventilator, radiation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Radiation Arm

Arm Description

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.

Outcomes

Primary Outcome Measures

Mortality rate of subjects treated with whole lung low-dose radiation

Death date of subjects will be collected from the date of radiation up to 1 month post radiation dose

Secondary Outcome Measures

Survival rate of subjects treated with whole lung low-dose radiation

Subject survival will be collected in number of days through 18 months post treatment

Change in number of Intensive care unit days

Number of intensive care days

Change in number of days using supplemental oxygen

Number of days using supplemental oxygen

Change in oxygenation index/oxygen saturation index for 14 days post treatment or until extubated

Oxygenation index/oxygen saturation until extubation

Quantitation of Lung Involvement using Chest CT

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

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

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

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

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.

Full Information

NCT ID

NCT04427566

First Posted

June 5, 2020

Last Updated

March 11, 2021

Sponsor

Ohio State University Comprehensive Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT04427566

Brief Title

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

Acronym

VENTED

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Unknown status

Study Start Date

July 23, 2020 (Actual)

Primary Completion Date

December 31, 2021 (Anticipated)

Study Completion Date

December 31, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Ohio State University Comprehensive Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID-19

Keywords

ventilator, radiation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Radiation Arm

Arm Type

Experimental

Arm Description

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 Type

Radiation

Intervention Name(s)

Radiation therapy

Other Intervention Name(s)

Linear accelerator, x-rays, LINAC

Intervention Description

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.

Primary Outcome Measure Information:

Title

Mortality rate of subjects treated with whole lung low-dose radiation

Description

Death date of subjects will be collected from the date of radiation up to 1 month post radiation dose

Time Frame

up to 28 days post radiation delivery

Secondary Outcome Measure Information:

Title

Survival rate of subjects treated with whole lung low-dose radiation

Description

Subject survival will be collected in number of days through 18 months post treatment

Time Frame

up to 18 months post radiation delivery

Title

Change in number of Intensive care unit days

Description

Number of intensive care days

Time Frame

up to 28 days post radiation delivery

Title

Change in number of days using supplemental oxygen

Description

Number of days using supplemental oxygen

Time Frame

up to 28 days post radiation delivery

Title

Change in oxygenation index/oxygen saturation index for 14 days post treatment or until extubated

Description

Oxygenation index/oxygen saturation until extubation

Time Frame

up to 28 days post radiation

Title

Quantitation of Lung Involvement using Chest CT

Description

Time Frame

up to 28 days post radiation

Title

Quantitation of Lung Opacities using Chest CT

Description

Time Frame

up to 28 days post radiation

Title

SARS-CoV2 viral titers

Description

Determine viral titers at baseline, days 7, 14 and 28.

Time Frame

up to 28 days

Title

Incidence of adverse events, including severity and duration, for administration of low dose radiation to lungs

Description

Review adverse events, including severity and duration, for all subjects to determine safety of the radiation treatment for pneumonia due to COVID-19.

Time Frame

up to 28 days

Title

Change in performance status after low dose radiation to lungs

Description

Time Frame

up to 28 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Arnab Chakravarti

Phone

614-293-0672

Arnab.Chakravarti@osumc.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Kimberly Mahler

Phone

614-685-4247

kimberly.mahler@osumc.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Arnab Chakravarti

Organizational Affiliation

James Cancer Hospital, Department of Radiation Oncology

Official's Role

Principal Investigator

Facility Information:

Facility Name

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Arnab Chakravarti, MD

Phone

614-293-8415

Arnab.Chakravarti@osumc.edu

First Name & Middle Initial & Last Name & Degree

Arnab Chakravarti, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32171076

Citation

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. Erratum In: Lancet. 2020 Mar 28;395(10229):1038. Lancet. 2020 Mar 28;395(10229):1038.

Results Reference

background

PubMed Identifier

32007143

Citation

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.

Results Reference

background

PubMed Identifier

24348219

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.

Results Reference

background

PubMed Identifier

17487675

Citation

Rodel F, Keilholz L, Herrmann M, Sauer R, Hildebrandt G. Radiobiological mechanisms in inflammatory diseases of low-dose radiation therapy. Int J Radiat Biol. 2007 Jun;83(6):357-66. doi: 10.1080/09553000701317358.

Results Reference

background

PubMed Identifier

16368644

Citation

Schaue D, Jahns J, Hildebrandt G, Trott KR. Radiation treatment of acute inflammation in mice. Int J Radiat Biol. 2005 Sep;81(9):657-67. doi: 10.1080/09553000500385556.

Results Reference

background

PubMed Identifier

32105637

Citation

Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J, Fan Y, Zheng C. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. 2020 Apr;20(4):425-434. doi: 10.1016/S1473-3099(20)30086-4. Epub 2020 Feb 24.

Results Reference

background

PubMed Identifier

31060383

Citation

Calabrese EJ, Dhawan G, Kapoor R, Kozumbo WJ. Radiotherapy treatment of human inflammatory diseases and conditions: Optimal dose. Hum Exp Toxicol. 2019 Aug;38(8):888-898. doi: 10.1177/0960327119846925. Epub 2019 May 6.

Results Reference

background

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

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