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Blood Ozonization in Patients With SARS-CoV-2 Respiratory Failure (CORMOR)

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: NCT04388514
Recruitment Status : Recruiting
First Posted : May 14, 2020
Last Update Posted : May 14, 2020
Sponsor:
Collaborators:
Fondazione Toscana Gabriele Monasterio
Policlinico Militare, Roma - Italy
Ospedale San Liberatore di Atri
Ospedale Umberto I di Torino
Università di Siena
Ospedale Civile di Lucca
Ospedale di Siracusa
Azienda Sanitaria Locale di Vercelli
Information provided by (Responsible Party):
Carlo Tascini, Azienda Sanitaria-Universitaria Integrata di Udine

Brief Summary:

Aim. The emerging outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. Beside the prescription of some promising drugs as chloroquine, azithromycin, antivirals (lopinavir/ritonavir, darunavir/cobicistat) and immunomodulating agents (steroids, tocilizumab), in our patients with mild to moderate pneumonia due to SARS-CoV-2 we planned a randomize study to evaluate, respect the best available therapy (BAT), the use of autohemotherapy treatement with an oxygen/ozone (O3) gaseous mixture as adjuvant therapy.

Design. Multicentric, randomized study.

Participants. Clinical presentations are based upon clinical phenotypes identified by the Italian Society of Emergency and Urgency Medicine (SIMEU - Società Italiana di Medicina di Emergenza-Urgenza) and patients that meet criteria of phenotypes 2 to 4 were treat with best available therapy (BAT), and randomized to receive or not O3-autohemotherapy.

Main outcome measures. The end-point were the time of respiratory improvement and earlier weaning from oxygen support: these parameters were included in the SIMEU clinical phenotypes classification.


Condition or disease Intervention/treatment Phase
SARS-CoV-2 Respiratory Failure Procedure: Medical Ozone procedure Not Applicable

Detailed Description:

Recruitment Details.

The investigator enrolled, in the study, subjects with COVID-19 modest to moderate respiratory insufficiency (SIMEU clinical phenotypes 2-4) thus cared in an infectious disease ward.

To note that The Italian Society of Emergency and Urgency Medicine (SIMEU - Società Italiana di Medicina di Emergenza-Urgenza) suggest to classified the COVID-19 patients in 5 clinical phenotypes:

  • Phenotype 1: subjects with fever and without respiratory failure (normal Arterial Blood Gas analysis - ABG -, six-minute walking test - 6mWT - and Chest XR). These patients usually can manage at home maintaining quarantine period.
  • Phenotype 2: subjects with fever but with ABG and/or Chest XR indicative of modest respiratory insufficiency (PO2> 60 mmHg in ambient air) and / or pulmonary consolidation area. These patients need to be hospitalized because they can get quickly worse.
  • Phenotype 3: subjects with fever associate to moderate-severe respiratory insufficiency (at triage PO2< 60 mmHg in ambient air) and /or bilateral pulmonary consolidation area at Chest XR. These patients need to be treated with high flow oxygen therapy.
  • Phenotype 4: subjects with respiratory failure with suspected ARDS (Adult Respiratory Distress Syndrome) or complicated pneumonia. These patients require hospitalization in sub-intensive care unit.
  • Phenotype 5: subject with ARDS at the beginning. These patients will require Intensive Care Unit (ICU) admission and non-invasive positive pressure ventilation (NIPPV) or mechanical ventilation.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

The study includes 2 arms:

  • Arm A: Blood ozonization plus BAT (n= 45 subjects)
  • Arm B: Standard of Care only without Blood ozonization (n= 45 subjects)

To note that the Standard of Care are therapy with antiretroviral therapy (lopinavir/ritonavir 2 tablets every 12 hours or darunavir/cobicistat 1 tablet per day) and hidrossycloroquine 400 mg every 12 hours then first day, followed by 200 mg every 12 hours for other 4 days

Masking: Single (Investigator)
Masking Description: Randomization, 1:1 ratio
Primary Purpose: Treatment
Official Title: Blood Ozonization in Patients With SARS-CoV-2 Respiratory Failure
Actual Study Start Date : April 8, 2020
Estimated Primary Completion Date : October 8, 2020
Estimated Study Completion Date : October 8, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Blood ozonization
Blood ozonization plus BAT
Procedure: Medical Ozone procedure
The systemic ozone treatment procedure was decided by the physician on duty and started preliminarily at the patient's bed with the drawing of autologous blood and, after proper O2/O3 mixing, with its re-infusion. After junction of an adequate venous patient's way with a dedicated latex free plastic bag containing 35 ml of sodium citrate, a blood amount of 200 ml is taken. At the end, the withdrawal line was washed and the re-infusion one was filled with saline solution. The blood, without any patient disconnection, was then mixed with a gas mixture of a 200 cc composed by 96% of Oxygen and 4% of Ozone with a therapeutic O3 range of 40 μg/mL of gas per mL of blood. In order to guarantee the O2/O3 homogeneous diffusion into the blood, the bag was gently mixed for about 10 minutes, therefore the blood was re-infused into the patients. The duration of ozone treatment lasted for 3 consecutive days.

No Intervention: Standard of Care

BAT "only"

To note that the BAT are therapy with antiretroviral therapy (lopinavir/ritonavir 2 tablets every 12 hours or darunavir/cobicistat 1 tablet per day) and hidrossycloroquine 400 mg every 12 hours then first day, followed by 200 mg every 12 hours for other 4 days.




Primary Outcome Measures :
  1. Time of respiratory improvement and earlier weaning from oxygen support [ Time Frame: 3 days ]
    Evaluation of ABG paramethers the day after the last blood ozonization procedure (Day 3)

  2. The time of respiratory improvement and earlier weaning from oxygen support [ Time Frame: 10 days ]
    Evaluation of ABG paramethers the one week after the last blood ozonization procedure (Day 10)


Secondary Outcome Measures :
  1. Assessment of the length of hospitalization [ Time Frame: up to 90 days ]
    Asse the lenghth of hospital stay in the two arms

  2. Assessment of the length of Intensive Care Unit (ICU) stay [ Time Frame: up to 90 days ]
    Asse the lenghth of ICU stay in the two arms

  3. Improvment in chest imaging finding [ Time Frame: 10 days ]
    improving, worsening or stability of the chest imaging (chest CT, Chest XR and/or Point-of-Care Ultrasound) finding in the two arms

  4. Improvment in cytokine release syndrome [ Time Frame: 10 days ]
    Evaluation of plasmatic cytochine (IL-6, lymphocyte typing for CD4, CD3, CD8, HLA-DR, CD45) response in the two arms



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and no pregnant female patients 18 years of age or older were eligible if they had a diagnostic specimen that was positive on RT-PCR, had pneumonia confirmed by chest imaging and gave their informed consent to participate at the study

Exclusion Criteria:

  • Exclusion criteria were pregnancy, G6PHD (glucose 6 phosphate dehydrogenase) deficiency, concomitant serious disease and failure to obtain informed consent.

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): NCT04388514


Contacts
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Contact: Carlo Tascini, MD +39 0432 559355 c.tascini@gmail.com
Contact: Emanuela Sozio, MD +39 emanuela.sozio@gmail.com

Locations
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Italy
Dott. Amato De Monte Recruiting
Udine, Italy
Contact: Amato De Monte, MD         
Sponsors and Collaborators
Azienda Sanitaria-Universitaria Integrata di Udine
Fondazione Toscana Gabriele Monasterio
Policlinico Militare, Roma - Italy
Ospedale San Liberatore di Atri
Ospedale Umberto I di Torino
Università di Siena
Ospedale Civile di Lucca
Ospedale di Siracusa
Azienda Sanitaria Locale di Vercelli
Investigators
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Study Chair: Amato De Monte Presidio Ospedaliero Universitario "Santa Maria della Misericordia", Udine - Italy
  Study Documents (Full-Text)

Documents provided by Carlo Tascini, Azienda Sanitaria-Universitaria Integrata di Udine:
Additional Information:
Publications:
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Responsible Party: Carlo Tascini, Infectious Diseases Department, Azienda Sanitaria-Universitaria Integrata di Udine
ClinicalTrials.gov Identifier: NCT04388514    
Other Study ID Numbers: CIG: Z7C2CA5837
First Posted: May 14, 2020    Key Record Dates
Last Update Posted: May 14, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: all IPD that underlie results in a publication
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: starting 6 months after publication
Access Criteria: Contacting the 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 Carlo Tascini, Azienda Sanitaria-Universitaria Integrata di Udine:
SARS-CoV-2
Respiratory Failure
COVID-19
medical ozone
ozone therapy
cytokine release syndrome
Additional relevant MeSH terms:
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Respiratory Insufficiency
Respiration Disorders
Respiratory Tract Diseases