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lack of recruitment
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| Name | Class |
|---|---|
| Hospital La Milagrosa | UNKNOWN |
| Hospital Vithas Valencia Consuelo | UNKNOWN |
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The host response against the coronavirus 2 (SARS-CoV-2) appears to be mediated by a 'cytoquine storm' developing a systemic inflammatory mechanism and an acute respiratory distress syndrome (ARDS), in the form of a bilateral pneumonitis, requiring invasive mechanical ventilation (IMV) in an important group of patients.
In terms of preventing progression to the critical phase with the consequent need of admission to the intensive care units (ICU), it has been recently proposed that this inflammatory cytoquine-mediated process can be safely treated by a single course of ultra-low radiotherapy (RT) dose < 1 Gy.
The main purpose of the study was to analyze the efficacy of ultra low-dose pulmonary RT, as an anti-inflammatory intention in patients with SARS-Cov-2 pneumonia with a poor or no response to standard medical treatment and without IMV.
The exceedingly high mortality rates of severe and critical COVID-19 warrant the evaluation of novel therapies that could potentially mitigate the advanced disease manifestations. In this context, is proposes a prospective multicenter study. It will include 15 patients, to assess the feasibility and efficacy of low-dose lung irradiation in COVID-19 pneumonia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| An experimental group receiving radiotherapy | Experimental | an experimental group with a poor or no response to standard medical treatment and without invasive mechanical ventilation (IMV) will receive ultra low-dose lung radiotherapy (0.8 Gy single dose) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ultra-Low-dose radiotherapy | Radiation | The total dose to be administered was 0.8 Gy in an only single session including both whole-lungs extended 1cm isometric in all directions. |
| Measure | Description | Time Frame |
|---|---|---|
| Oxygen Therapy Status at Day 2 | To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).) | At 2 after RT |
| Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 2 | To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement) | At 2 days after RT |
| Measure | Description | Time Frame |
|---|---|---|
| Blood Gas Analysis at Day 2 | Pa02 / Fi02 > 300 mmHg | At 2 days after RT |
| Blood Test at Day 2 | Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen) |
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Inclusion Criteria:
Age > 18 years-old.
Diagnosis of pneumonia due to COVID-19 serologically proven by polymerase chain reaction (PCR) or highly suspected to be COVID-related.
Charlson Comorbidity Index (CCI) less than 6 score.
Poor or no response to standard medical treatment, based on:
*% Sat02 <93%
Eastern Cooperative Oncology Group (ECOG) Status < or = 3
Life expectancy (LE)> 1 month at hospital admission for COVID-19
No previous thoracic RT (relative-individualization criteria) or chemotherapy (chemoinduced pulmonary toxicity, eg Bleomycin).
Verbal information on the procedure, objective and secondary effects, acceptance and signing of informed consent by the patient or legal guardian.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Escarlata López RamÃrez, MD, PhD | Fundacion GenesisCare | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital La Milagrosa, GenesisCare | Madrid | 28010 | Spain | |||
| Hospital Vithas Valencia Consuelo |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32342871 | Result | Kirkby C, Mackenzie M. Is low dose radiation therapy a potential treatment for COVID-19 pneumonia? Radiother Oncol. 2020 Jun;147:221. doi: 10.1016/j.radonc.2020.04.004. Epub 2020 Apr 6. No abstract available. | |
| 1750226 | Result | Berk LB, Hodes PJ. Roentgen therapy for infections: an historical review. Yale J Biol Med. 1991 Mar-Apr;64(2):155-65. |
| Label | URL |
|---|---|
| Li, K., Fang, Y., Li, W. et al. CT image visual quantitative evaluation and clinical classification of coronavirus disease (COVID-19). Eur Radiol (2020). https://doi.org/10.1007/s00330-020-06817-6 | View source |
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Medical history and biographical and clinical data of each patient will be recorded and shared.
The overall results of any research conducted will be available on study data publication.
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an experimental group will receive ultra low-dose lung radiotherapy
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| ventilatory support with oxygen therapy | Device | Oxygen Therapy: Nasal Cannula (NC); Ventimask (VMK) or VMK with reservoir |
|
| Lopinavir/ritonavir | Drug | 100/400 mg/12h; 7-10 days |
|
|
| Hydroxychloroquine | Drug | 200 mg/12h |
|
|
| Azithromycin | Drug | 500 mg/24h, 3 days |
|
| Piperacillin/tazobactam | Drug | 4 g / 0.5 g administered every 6-8 hours through a vein (directly into the bloodstream), for 5-14 days. Adjustment to kidney function |
|
| Low molecular weight heparin | Drug | prophylactic doses |
|
| Corticosteroid injection | Drug | 250mg x 3 boluses |
|
|
| Tocilizumab | Drug | 600mg single dose |
|
| At 2 days after RT |
| Oxygen Therapy Status at Day 5 | To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).) | At 5 after RT |
| Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 5 | To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement) | At 5 days after RT |
| Blood Test at Day 5 | Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen) | At 5 days after RT |
| Oxygen Therapy Status at Day 7 | To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).) | At 7 after RT |
| Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 7 | To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement) | At 7 days after RT |
| Blood Test at Day 7 | Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen) | At 7 days after RT |
| Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan at Day 7 | To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points) | At 7 days after RT |
| Recovery time | Recovery time after RT administration until hospital discharge or death (<48h; 2-7 days; >7 days; clinical worsening or death) | From RT administration until hospital discharge or death |
| COVID-19 status | COVID-19 negativization test | At 7 days after RT |
| Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan al Month 1 | To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points) | At 1 month after RT |
| Acute Toxicity | Toxicity was assessed and rated according to the NIH Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and RTOG scales. | 1-3 months after RT |
| Valencia |
| 46007 |
| Spain |
| 24348219 | Result | 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. |
| 31933547 | Result | Cuttler JM. Application of Low Doses of Ionizing Radiation in Medical Therapies. Dose Response. 2020 Jan 6;18(1):1559325819895739. doi: 10.1177/1559325819895739. eCollection 2020 Jan-Mar. |
| 22907572 | Result | Arenas M, Sabater S, Hernandez V, Rovirosa A, Lara PC, Biete A, Panes J. Anti-inflammatory effects of low-dose radiotherapy. Indications, dose, and radiobiological mechanisms involved. Strahlenther Onkol. 2012 Nov;188(11):975-81. doi: 10.1007/s00066-012-0170-8. Epub 2012 Aug 22. |
| 31060383 | Result | 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. |
| 17487675 | Result | 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. |
| 16368644 | Result | 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. |
| 32140081 | Result | Torres Royo L, Antelo Redondo G, Arquez Pianetta M, Arenas Prat M. Low-Dose radiation therapy for benign pathologies. Rep Pract Oncol Radiother. 2020 Mar-Apr;25(2):250-254. doi: 10.1016/j.rpor.2020.02.004. Epub 2020 Feb 22. |
| 32373721 | Result | Lara PC, Burgos J, Macias D. Low dose lung radiotherapy for COVID-19 pneumonia. The rationale for a cost-effective anti-inflammatory treatment. Clin Transl Radiat Oncol. 2020 Apr 25;23:27-29. doi: 10.1016/j.ctro.2020.04.006. eCollection 2020 Jul. |
| 33502567 | Derived | Moreno-Olmedo E, Suarez-Gironzini V, Perez M, Filigheddu T, Minguez C, Sanjuan-Sanjuan A, Gonzalez JA, Rivas D, Gorospe L, Larrea L, Lopez E. COVID-19 pneumonia treated with ultra-low doses of radiotherapy (ULTRA-COVID study): a single institution report of two cases. Strahlenther Onkol. 2021 May;197(5):429-437. doi: 10.1007/s00066-020-01743-4. Epub 2021 Jan 27. |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D000080424 | Cytokine Release Syndrome |
| D012128 | Respiratory Distress Syndrome |
| ID | Term |
|---|---|
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
| D012120 | Respiration Disorders |
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| ID | Term |
|---|---|
| D010102 | Oxygen Inhalation Therapy |
| D061466 | Lopinavir |
| C558899 | lopinavir-ritonavir drug combination |
| D006886 | Hydroxychloroquine |
| D017963 | Azithromycin |
| D000077725 | Piperacillin, Tazobactam Drug Combination |
| D006495 | Heparin, Low-Molecular-Weight |
| D000305 | Adrenal Cortex Hormones |
| D008775 | Methylprednisolone |
| C502936 | tocilizumab |
| ID | Term |
|---|---|
| D012138 | Respiratory Therapy |
| D013812 | Therapeutics |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D002738 | Chloroquine |
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D000078142 | Tazobactam |
| D010397 | Penicillanic Acid |
| D010406 | Penicillins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D010878 | Piperacillin |
| D000667 | Ampicillin |
| D010400 | Penicillin G |
| D013457 | Sulfur Compounds |
| D013450 | Sulfones |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D006493 | Heparin |
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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