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
| Registry | NCT04427566, acronym VENTED |
|---|---|
| Status | Terminated - there were very few patients using ventilators, so it was impossible to enroll additional subjects |
| Phase | Phase 2 |
| Study type | Interventional; na, single group, masking: none, treatment |
| Enrollment | 2 (Actual) |
| Sponsor | Ohio State University (Other) |
| Conditions | COVID-19 |
| Interventions | Radiation therapy (Radiation) |
| Dates | start 2020-07-23, primary completion 2021-04-26, completion 2021-04-26, first posted 2020-06-11, last updated 2026-08-19 |
| Locations | 1 site in United States |
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All trials for COVID-19 All trials of Radiation therapy
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.
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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Radiation Arm | Experimental | Radiation: Radiation therapy | 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. |
Sex: All, ages: 18 Years to any
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
| Milestone | Radiation Arm |
|---|---|
| Started | 2 |
| Completed | 1 |
| Not completed | 1 |
Time frame: Adverse Events were collected after administration of radiation, until 9 months post treatment. Patient then moved and was lost to followup for the 1 year evaluation.
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|---|---|---|
| Radiation Arm | 0/1 (0.0%) | 1/1 (100.0%) | 1/1 (100.0%) |
| Term | Organ system | Radiation Arm |
|---|---|---|
| hypokalemia | Metabolism and nutrition disorders | 1/1 |
| hypoxia | Respiratory, thoracic and mediastinal disorders | 1/1 |
| capillary leak syndrome | Vascular disorders | 1/1 |
| hypotension | Vascular disorders | 1/1 |
| acute kidney injury | Renal and urinary disorders | 1/1 |
| Term | Organ system | Radiation Arm |
|---|---|---|
| head wound | Musculoskeletal and connective tissue disorders | 1/1 |
| hypotension | Vascular disorders | 1/1 |
| delerium | Psychiatric disorders | 1/1 |
| capillary leak syndrome | Vascular disorders | 1/1 |
| hypokalemia | Metabolism and nutrition disorders | 1/1 |
| hypoalbuminemia | Metabolism and nutrition disorders | 1/1 |
| hypophosphatemia | Metabolism and nutrition disorders | 1/1 |
| hematoma | Vascular disorders | 1/1 |
| decreased platelet count | Investigations | 1/1 |
| increased alkaline phosphatase | Investigations | 1/1 |
| hyperphosphatemia | Metabolism and nutrition disorders | 1/1 |
| anemia | Blood and lymphatic system disorders | 1/1 |
| hypokalemia | Metabolism and nutrition disorders | 1/1 |
| trace edema | General disorders | 1/1 |
| increased creatinine | Investigations | 1/1 |
| proteinuria | Renal and urinary disorders | 1/1 |
| hyperkalemia | Metabolism and nutrition disorders | 1/1 |
| decreased lymphocyte count | Investigations | 1/1 |
| pain | Musculoskeletal and connective tissue disorders | 1/1 |
| infection, bronchial | Infections and infestations | 1/1 |
| nausea | Gastrointestinal disorders | 1/1 |
| vomiting | Gastrointestinal disorders | 1/1 |
| urinary retention | Renal and urinary disorders | 1/1 |
| diarrhea | Gastrointestinal disorders | 1/1 |
| abdominal pain | Gastrointestinal disorders | 1/1 |
| Cholelithiasis | Gastrointestinal disorders | 1/1 |
| voice alteration | Respiratory, thoracic and mediastinal disorders | 1/1 |
| back pain | Musculoskeletal and connective tissue disorders | 1/1 |
| orthopenia | Respiratory, thoracic and mediastinal disorders | 1/1 |
| insomnia | Psychiatric disorders | 1/1 |
Limitations and caveats: Difficult to enroll patients to the study due to their delicate medical state and population limitations. The number of eligible patients on ventilators decreased after first year of study.
| Facility | City | Country | Status |
|---|---|---|---|
| Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center | Columbus, Ohio | United States |