Safety and Efficacy of Nebulised Anti-Inflammatory Solution of Alkaline Hypertonic Ibuprofen (AHI) for Treatment of SARS-Cov-2 Infection: A Compassionate Study with a Comparator Arms

Abstract

Background. This retrospective study evaluates the efficacy of inhalation therapy with alkaline hypertonic ibuprofen (AHI) in COVID-19 positive patients compared to a control group of patients who received conventional treatment. The study was carried out at the Orías Hospital in Jujuy Province, Argentina, from June to September 2020, with final follow-up on September 30. Methods. The study included 99 COVID-19 positive patients with moderate to severe disease (respiratory distress and/or hypoxemia). The control group of 62 patients were treated with the protocols in force at that time, oxygen, dexamethasone and enoxaparin. The group under evaluation comprised 37 patients treated with AH), in addition to standard treatment. Findings. Result shows that the treatment with AHI formulation is safe and effective. The mean respiratory rate (RR) of the patients went from 26.3 before treatment with AHI to 19.8 after treatment. On the other hand, the O2 saturation of patients before treatment with AHI showed a mean of 89.0%; at the end of treatment, the mean was 95.8%. In patients treated with AHI, on day 14, 85% had been discharged, while in patients not treated with AHI, only 36-37% were discharged on day 23. Patients with standard treatment, without AHI, show a mortality of 38.7%, distributed evenly in the 25 days of hospitalization. The mortality of patients treated with AHI was 8.1%, observed within the first 10 days of hospitalization. Interpretation. Results show that nebulization with AHI is an anti-inflammatory therapeutic alternative for the treatment of COVID-19 positive patients.

Repurposing Inhaled Ibuprofenate, a Non Steroidal Anti‐Inflammatory Drug, as a Potential Adjuvant Treatment for Pneumonia, CARDS and its Aetiological Agent SARS‐CoV‐2

“…5 Three retrospective observational studies have been carried out in Argentina with NaIHS in moderate and severe COVID-19 pneumonia. The first study analysed data from 99 patients 3 and the second study analysed data from 383 patients (15% mechanically ventilated), 4 both showing similar preliminary results: a significant reduction in mortality, improvement of clinical outcomes, rapid reversal of hypoxaemia and decrease in hospitalization stay in pneumonia and COVID-19-associated acute respiratory distress syndrome (CARDS). 3,4 The third and most relevant study, conducted with the approval of the Institutional Review Board of the National Bureau of Economic Research of Harvard and Columbia Universities, 5 analysed data from 5146 patients 5 and concluded that NaIHS reduces mortality by 48.7%.…”

“…1 As previously exposed, NaIHS has been used in moderate and severe COVID-19 pneumonia, in the modality of compassionate use and covered by the Declaration of Helsinki. [3][4][5] Accordingly, it was approved for emergency use in several Argentine provinces and its phase II clinical trial (Pegasus trial) was approved in July 2021, by the Drug, Food and Technology National Administration of Argentina. 5 Three retrospective observational studies have been carried out in Argentina with NaIHS in moderate and severe COVID-19 pneumonia.…”

“…11 The R-ibuprofen enantiomer shows in vivo an extensive interconversion into the S-ibuprofen enantiomer, which is considered to be the pharmacologically active form 13 and furthermore, ibuprofen continues to date with still poorly understood COX-independent effects. 11 The hydrosoluble NaIHS formulation administered by inhalation bears the following characteristics: it is slightly alkaline, it has high ionic strength (due to the association with hypertonic sodium chloride, which stabilises and strengthens the formulation) and it has a micrometric or nanometric size, 1,3 thus achieving a high concentration in the pulmonary biophase since, being hydrosoluble, NaIHS requires a dose 10 times lower compared to traditional orally administered ibuprofen to achieve its therapeutic effect and may also have a high pulmonary volume of distribution, 1 thus obtaining a high therapeutic safety and equal pharmacological effect at very low NaIHS doses of 150 mg/day, distributed in three aerosolisations of 50 mg every 8 h (with the possibility of increasing the dose if necessary), 1,4 using special nebulisation devices that avoid aerosolisation and contagion of health personnel. 1 In a study conducted with the pharmacokinetic objective of evaluating the effectiveness of semifluorinated alkanes as potential drug carriers in nebulisable aerosols, semifluorinated alkanes (perfluorohexyloctane) have occasionally been therein associated with ibuprofen.…”

Blocking the action of NLRP3 inflammasome by inhaled ibuprofenate on pulmonary macrophages infected by SARS‐CoV‐2

“…Currently, there are available three observational studies in the compassionate use modality in moderate and severe Coronavirus Disease 2019 (COVID-19) pneumonia, carried out in Argentina, [1][2][3] with all three studies concluding that there was a significant reduction in mortality. [1][2][3] The most recent of these was conducted with the approval of the Institutional Review Board of the National Bureau of Economic Research (NBER) of Harvard and Columbia Universities, which analysed data from 5146 patients and concluded that NaIHS reduced mortality by 48.7%, 3 although randomized clinical trials are steel needed to confirm these data.…”