Inhaled Ibuprofen to Treat COVID-19 (CórdobaTrail)

• ClinicalTrials.gov Identifier: NCT04382768
• Recruitment Status: Recruiting
• First Posted: May 11, 2020
• Last Update Posted: June 11, 2020
• Sponsor: Química Luar SRL
• Collaborators: National Council of Scientific and Technical Research, Argentina; Centro de Excelencia en Productos y Procesos Córdoba
• Information provided by (Responsible Party): Néstor H García, National Council of Scientific and Technical Research, Argentina

Tracking Information

• First Submitted Date: May 6, 2020
• First Posted Date: May 11, 2020
• Last Update Posted Date: June 11, 2020
• Actual Study Start Date: May 1, 2020
• Estimated Primary Completion Date: January 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 7, 2020)

• Change in the scale of ordinary COVID results at 7, 14 and 28 days in patients with acute respiratory infection, induced by SARS-CoV-2, treated with inhaled Ibuprofen. [ Time Frame: 7, 14 and 28 days ]
  Time to clinical improvement: defined as time from inhaled Ibuprofen first dose to an improvement of three points from the status on a seven-category ordinary scale
• Change to Negativization of the swab to the following treatment points on day 7, day 14, 21 and 28 after treatment with inhaled Ibuprofen. [ Time Frame: 7, 14 and 28 days ]
  Negativization of two consecutive pharyngo-nasal swab 24-72 hrs apart

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 7, 2020)

• Chage in length of Hospital stay [ Time Frame: 28 days ]
• Chage in duration of ventilation [ Time Frame: 28 days ]
• Chage in length of Critical Care stay [ Time Frame: 28 days ]
• Average score of National Early Warning (NEWS2) between days 1, 7, 14 and 28. [ Time Frame: 1, 7, 14 and 28 ]
  NEWS2 score 20 points is the maximum and indicates that the patient needs emergent assessment by a clinical team or critical care team and usually transfer to higher level of care.
• Average change in quick sepsis-related organ failure assessment score (qSOFA) score between day 1, 7, 14 and 28. [ Time Frame: 1, 7, 14 and 28 days ]
  qSOFA, score for sepsis, a maximum value of 3 indicates high risk qSOFA Scores 2-3 are associated with a 3- to 14-fold increase in in-hospital mortality. Assess for evidence of organ dysfunction with blood testing including serum lactate and calculation of the full SOFA Score. Patients meeting these qSOFA criteria should have infection considered even if it was previously not.
• Time from first dose to conversion to normal or mild pneumonia [ Time Frame: 28 days ]
• Antibiotic requirement [ Time Frame: 28 days ]
• Glucocorticoids requirement [ Time Frame: 28 days ]
• Incidence of adverse event [ Time Frame: 28 days ]
• Incidence of serious adverse event [ Time Frame: 28 days ]
• Number of deaths from any cause at 28 days [ Time Frame: 28 days ]
• Lymphocyte count [ Time Frame: 28 days ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Inhaled Ibuprofen to Treat COVID-19
• Official Title: Extended Compassionate Use Program (UCA) With Inhalational Ibuprofen in Patients With Acute Respiratory Pathology, Mediated by COVID-19.
• Brief Summary: The study aims to evaluate the reduction in severity and progression of lung injury with inhaled ibuprofen in patients with severe acute respiratory syndrome due to SARS-CoV-2 virus.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

This is an expanded compassionate use program for patients infected with SARS-CoV-2. All patients or their legally authorized representative must provide written informed consent and the patient will be examined to assess their eligibility. Eligible patients will receive inhalation ibuprofen ate three times a day, plus standard care, until the patient became negative, or their physician considers enough or the patient requested to stop.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Coronavirus Infection
• Respiratory Disease
• SARS (Disease)

Intervention

Drug: Inhaled Hypertonic ibuprofen

Standard of care plus lipid ibuprofen 50mg tid

Study Arms

Experimental: Luarprofen

Inhaled Hypertonic ibuprofen 50 mg tid

Intervention: Drug: Inhaled Hypertonic ibuprofen

Publications *

• Muñoz AJ, Alasino RV, Garro AG, Heredia V, García NH, Cremonezzi DC, Beltramo DM. High Concentrations of Sodium Chloride Improve Microbicidal Activity of Ibuprofen against Common Cystic Fibrosis Pathogens. Pharmaceuticals (Basel). 2018 May 17;11(2). pii: E47. doi: 10.3390/ph11020047.
• He L, Ding Y, Zhang Q, Che X, He Y, Shen H, Wang H, Li Z, Zhao L, Geng J, Deng Y, Yang L, Li J, Cai J, Qiu L, Wen K, Xu X, Jiang S. Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS. J Pathol. 2006 Nov;210(3):288-97.
• Veljkovic V, Vergara-Alert J, Segalés J, Paessler S. Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target. Version 4. F1000Res. 2020 Jan 27 [revised 2021 Jan 1];9:52. doi: 10.12688/f1000research.22149.4. eCollection 2020.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 7, 2020): 40
• Original Actual Enrollment: Same as current
• Estimated Study Completion Date: January 2021
• Estimated Primary Completion Date: January 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Provision of written informed consent by the patient OR by the patient's Legal Representative.
2. Confirmed or suspected SARS-CoV-2 infection;
3. Pneumonia without criteria of severity.

4. With some of the following conditions:

   • Diabetes.
   • Cardiovascular disease.
   • Chronic kidney disease.
   • Chronic obstructive pulmonary disease.
   • Structural diseases of the lung
   • Immunocompromise.
5. Patient who presents negative results by rtPCR for SARS CoV-2, in case of being highly suspicious, the patient may receive it empirically until the results are obtained.
6. No unstable bronchial asthma

Exclusion Criteria:

1. The doctor considers that participation in the Program is not the best for patients or for any condition that prevents the Program from being followed safely.
2. Patients with a history of unstable bronchial asthma
3. The patient is allergic to ibuprofen or any of the compounds in the preparation.
4. Hypersensitivity to the drug, nasal polyps syndrome, angioedema or bronchospasm against aspirin or other NSAIDs.
5. Pregnant or lactating woman, or positive pregnancy test on a pre-dose exam.
6. Patient who is expected to be transferred to another place other than the place where the Program starts, within 7 days of starting it.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Dante M Beltramo, PhD; 54 9 351 766-8050; dantemiguelbeltramo@gmail.com

Contact: Nestor H García, MD, PhD; 5493513539948; garcia.nestor@conicet.gov.ar

• Listed Location Countries: Argentina

Administrative Information

• NCT Number: NCT04382768
• Other Study ID Numbers: DNL000004
• 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: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Responsible Party: Néstor H García, National Council of Scientific and Technical Research, Argentina
• Study Sponsor: Química Luar SRL

Collaborators

• National Council of Scientific and Technical Research, Argentina
• Centro de Excelencia en Productos y Procesos Córdoba

Investigators

• Study Director: Dante M Beltramo, PhD; Centro de Excelencia en Productos y Procesos Córdoba

• PRS Account: Química Luar SRL
• Verification Date: June 2020