scholarly journals Auxora Versus Standard of Care For The Treatment of Severe or Critical COVID-19 Pneumonia: Results From A Randomized Controlled Trial

2020 ◽  
Author(s):  
Joseph Miller ◽  
Charles Bruen ◽  
Michael Schnaus ◽  
Jeffrey Zhang ◽  
Sadia Ali ◽  
...  
Keyword(s):  
Standard Of Care ◽  
Ordinal Scale ◽  
Controlled Study ◽  
Respiratory Complications ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Randomized Controlled ◽  
Crac Channel ◽  
The Impact

Abstract BACKGROUND: Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumonia METHODS: A randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia. Patients were randomized 2:1 to receive three doses of once-daily Auxora versus standard of care (SOC) alone. The primary objective was to assess safety and tolerability of Auxora. Following FDA guidance, study enrollment was halted early to allow for transition to a randomized, blinded, placebo-controlled study. RESULTS: In total, 17 patients with severe and three with critical COVID-19 pneumonia were randomized to Auxora and nine with severe and one with critical COVID-19 pneumonia to SOC. Similar proportions of patients receiving Auxora and SOC experienced ≥1 adverse event (75% versus 80%, respectively). Fewer patients receiving Auxora experienced serious adverse events versus SOC (30% versus 50%, respectively). Two patients (10%) receiving Auxora and two (20%) receiving SOC died in the 30 days after randomization. Among patients with severe COVID-19 pneumonia, median time to recovery with Auxora was five days versus 12 days with SOC; recovery rate ratio was 1.87 (95%CI, 0.72, 4.89). Invasive mechanical ventilation was needed in 18% of patients with severe COVID-19 pneumonia receiving Auxora versus 50% receiving SOC (absolute risk reduction=32%; 95%CI, -0.07, 0.71). Outcomes measured by an 8-point ordinal scale were significantly improved for patients receiving Auxora, especially for patients with a baseline PaO2/FiO2=101-200. CONCLUSIONS: Auxora demonstrated a favorable safety profile in patients with severe or critical COVID-19 pneumonia and improved outcomes in patients with severe COVID-19 pneumonia. These results, however, are limited by the open-label study design and small patient population resulting from early cessation of enrollment in response to regulatory guidance. The impact of Auxora on respiratory complications in patients with severe COVID-19 pneumonia will be further assessed in a planned randomized, blinded, placebo-controlled study. Trial registration: ClinicalTrials.gov, NCT04345614. Submitted 7April2020 - https://clinicaltrials.gov/ct2/show/NCT04345614

scholarly journals Auxora Versus Standard of Care For The Treatment of Severe or Critical COVID-19 Pneumonia: Results From A Randomized Controlled Trial

2020 ◽  
Author(s):  
Joseph Miller ◽  
Charles Bruen ◽  
Michael Schnaus ◽  
Jeffrey Zhang ◽  
Sadia Ali ◽  
...  
Keyword(s):  
Standard Of Care ◽  
Ordinal Scale ◽  
Controlled Study ◽  
Respiratory Complications ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Randomized Controlled ◽  
Crac Channel ◽  
The Impact

Abstract BACKGROUND: Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumonia METHODS: A randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia. Patients were randomized 2:1 to receive three doses of once-daily Auxora versus standard of care (SOC) alone. The primary objective was to assess safety and tolerability of Auxora. Following FDA guidance, study enrollment was halted early to allow for transition to a randomized, blinded, placebo-controlled study. RESULTS: In total, 17 patients with severe and three with critical COVID-19 pneumonia were randomized to Auxora and nine with severe and one with critical COVID-19 pneumonia to SOC. Similar proportions of patients receiving Auxora and SOC experienced ≥1 adverse event (75% versus 80%, respectively). Fewer patients receiving Auxora experienced serious adverse events versus SOC (30% versus 50%, respectively). Two patients (10%) receiving Auxora and two (20%) receiving SOC died in the 30 days after randomization. Among patients with severe COVID-19 pneumonia, median time to recovery with Auxora was five days versus 12 days with SOC; recovery rate ratio was 1.87 (95%CI, 0.72, 4.89). Invasive mechanical ventilation was needed in 18% of patients with severe COVID-19 pneumonia receiving Auxora versus 50% receiving SOC (absolute risk reduction=32%; 95%CI, -0.07, 0.71). Outcomes measured by an 8-point ordinal scale were significantly improved for patients receiving Auxora, especially for patients with a baseline PaO2/FiO2=101-200. CONCLUSIONS: Auxora demonstrated a favorable safety profile in patients with severe or critical COVID-19 pneumonia and improved outcomes in patients with severe COVID-19 pneumonia. These results, however, are limited by the open-label study design and small patient population resulting from early cessation of enrollment in response to regulatory guidance. The impact of Auxora on respiratory complications in patients with severe COVID-19 pneumonia will be further assessed in a planned randomized, blinded, placebo-controlled study. Trial registration: ClinicalTrials.gov, NCT04345614. Submitted 7April2020 - https://clinicaltrials.gov/ct2/show/NCT04345614

scholarly journals Auxora Versus Standard of Care For The Treatment of Severe or Critical COVID-19 Pneumonia: Results From A Randomized Controlled Trial

2020 ◽  
Author(s):  
Joseph Miller ◽  
Charles Bruen ◽  
Michael Schnaus ◽  
Jeffrey Zhang ◽  
Sadia Ali ◽  
...  
Keyword(s):  
Standard Of Care ◽  
Ordinal Scale ◽  
Controlled Study ◽  
Respiratory Complications ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Randomized Controlled ◽  
Crac Channel ◽  
The Impact

Abstract BACKGROUND: Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumonia METHODS: A randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia. Patients were randomized 2:1 to receive three doses of once-daily Auxora versus standard of care (SOC) alone. The primary objective was to assess safety and tolerability of Auxora. Following FDA guidance, study enrollment was halted early to allow for transition to a randomized, blinded, placebo-controlled study. RESULTS: In total, 17 patients with severe and three with critical COVID-19 pneumonia were randomized to Auxora and nine with severe and one with critical COVID-19 pneumonia to SOC. Similar proportions of patients receiving Auxora and SOC experienced ≥1 adverse event (75% versus 80%, respectively). Fewer patients receiving Auxora experienced serious adverse events versus SOC (30% versus 50%, respectively). Two patients (10%) receiving Auxora and two (20%) receiving SOC died in the 30 days after randomization. Among patients with severe COVID-19 pneumonia, median time to recovery with Auxora was five days versus 12 days with SOC; recovery rate ratio was 1.87 (95%CI, 0.72, 4.89). Invasive mechanical ventilation was needed in 18% of patients with severe COVID-19 pneumonia receiving Auxora versus 50% receiving SOC (absolute risk reduction=32%; 95%CI, -0.07, 0.71). Outcomes measured by an 8-point ordinal scale were significantly improved for patients receiving Auxora, especially for patients with a baseline PaO2/FiO2=101-200. CONCLUSIONS: Auxora demonstrated a favorable safety profile in patients with severe or critical COVID-19 pneumonia and improved outcomes in patients with severe COVID-19 pneumonia. These results, however, are limited by the open-label study design and small patient population resulting from early cessation of enrollment in response to regulatory guidance. The impact of Auxora on respiratory complications in patients with severe COVID-19 pneumonia will be further assessed in a planned randomized, blinded, placebo-controlled study. Trial registration: ClinicalTrials.gov, NCT04345614. Submitted 7April2020 - https://clinicaltrials.gov/ct2/show/NCT04345614

scholarly journals Auxora Versus Standard of Care for the Treatment of Severe or Critical COVID-19 Pneumonia: Results from a Randomized Controlled Trial

2020 ◽  
Author(s):  
Joseph Miller ◽  
Charles Bruen ◽  
Michael Schnaus ◽  
Jeffrey Zhang ◽  
Sadia Ali ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Absolute Risk ◽  
Controlled Trial ◽  
Invasive Mechanical Ventilation ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Respiratory Complications ◽  
Randomized Controlled ◽  
Crac Channel ◽  
The Impact

Abstract BACKGROUNDCalcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumoniaMETHODSA randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia. Patients were randomized 2:1 to receive three doses of once-daily Auxora versus standard of care (SOC) alone. The primary objective was to assess safety and tolerability of Auxora. Additional outcomes included changes in clinical status based on an 8-point ordinal scale and the proportion of patients dying or requiring invasive mechanical ventilation in the 30 days after randomization.RESULTSIn total, 17 patients with severe and three with critical COVID-19 pneumonia were randomized to Auxora and nine with severe and one with critical COVID-19 pneumonia to SOC. Similar proportions of patients receiving Auxora and SOC experienced ≥1 adverse event (75% versus 80%, respectively). Fewer patients receiving Auxora experienced serious adverse events versus SOC (30% versus 50%, respectively). Two patients (10%) receiving Auxora and two (20%) receiving SOC died in the 30 days after randomization. Among patients with severe COVID-19 pneumonia, median time to recovery with Auxora was five days versus 12 days with SOC; recovery rate ratio was 1.87 (95%CI, 0.72, 4.89). Invasive mechanical ventilation was needed in 18% of patients with severe COVID-19 pneumonia receiving Auxora versus 50% receiving SOC (absolute risk reduction=32%; 95%CI, -0.07, 0.71). One intubation or death over 30 days would be prevented by treating 2.6 patients with Auxora. Outcomes measured by an 8-point ordinal scale were significantly improved for patients receiving Auxora, especially for patients with a baseline PaO2/FiO2=101-200.CONCLUSIONSAuxora demonstrated a favorable safety profile in patients with severe or critical COVID-19 pneumonia and improved outcomes in patients with severe COVID-19 pneumonia. The impact of Auxora on respiratory complications in patients with severe COVID-19 pneumonia will be further assessed in a planned randomized, blinded, placebo-controlled study.TRIAL REGISTRATIONClinicalTrials.gov,NCT04345614. Retrospectively registered 14April2020 - https://clinicaltrials.gov/ct2/show/NCT04345614

scholarly journals Prospective, Randomized, Parallel-Group, Open-Label Study to Evaluate the Efficacy and Safety of IMU-838, in Combination with Oseltamivir, in Adults with Coronavirus Disease 19 The IONIC Trial

2021 ◽  
Author(s):  
Kavi Sharma ◽  
Dr Lisa Berry ◽  
Dr Evangelos Vryonis ◽  
Dr Asad Ali ◽  
Dr Beatriz Lara ◽  
...  
Keyword(s):  
Clinical Improvement ◽  
Trial Design ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Therapeutic Effects ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Link Type ◽  
Discharge From Hospital

Background: Globally there is a scarcity of effective treatments for SARS-CoV-2 infections (causing COVID 19). Repurposing existing medications may offer the best hope for treating COVID 19 patients to curb the pandemic. IMU-838 is a dihydroorotate dehydrogenase (DHODH) inhibitor, which is an effective mechanism for antiviral effects against respiratory viruses. When used synergistically with Oseltamivir, therapeutic effects have been observed against influenza and SARS-CoV-2 in rodents.(13) The IONIC trial is a randomized control trial that will investigate whether time to clinical improvement in COVID 19 patients is improved following a 14 day course of IMU-838 + Oseltamivir versus Oseltamivir alone. Methods: IONIC trial is an open label study in which participants will be randomised 1:1 in two parallel arms; the intervention arm (IMU-838 + Oseltamivir) and control arm (Oseltamivir only). The primary outcome is time-to-clinical improvement; defined as the time from randomisation to: a 2-point improvement on WHO ordinal scale; discharge from hospital, or death (whichever occurs first). The study is sponsored by UHCW NHS Trust and funded by LifeArc. Discussion: The IONIC Protocol describes an overarching trial design to provide reliable evidence on the efficacy of IMU-838 (vidofludimus calcium) when delivered in combination with an antiviral therapy (Oseltamivir) [IONIC Intervention] for confirmed or suspected COVID-19 infection in adult patients receiving usual standard of care. Trial Registration: The trial was registered with EudraCT (2020-001805-21) on 09.04.2020 and ISRCTN on 23.09.2020 (ISRCTN53038326) and Clinicaltrials.gov on 17.08.2020 (NCT04516915) Strengths and Limitations: This study is the first to recruit participants in the trial exploring the effectiveness of IMU-838 in COVID-19. In addition, we believe it is the only trial exploring the effectiveness of IMU-838 in combination with Oseltamivir (Tamiflu) in patients with moderate to severe COVID-19. However, to make the trial design flexible due to the on-going pandemic the trial is un-blinded.

scholarly journals Effectiveness and Impact of Capsaicin 8% Patch on Quality of Life in Patients with Lumbosacral Pain: An Open-label Study

2016 ◽  
Vol 7;19 (7;9) ◽  
pp. E1049-E1053 ◽  
Author(s):  
Panagiotis Zis
Keyword(s):  
Quality Of Life ◽  
Neuropathic Pain ◽  
Care Center ◽  
Controlled Study ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Vas Score ◽  
The Impact

Background: Capsaicin 8% patch (Qutenza™) is mainly used to treat postherpetic neuralgia and HIV-associated neuropathy. Evidence of the efficacy of Qutenza in other forms of neuropathic pain is lacking. Objective: To evaluate the analgesic effect and the impact on quality of life after a single application of the capsaicin 8% cutaneous patch in patients with lumbosacral pain. Study Design: Prospective open-label study of capsaicin 8% patch in patients with lumbosacral pain. Setting: Outpatient Pain and Palliative Care Center. Methods: All recruited patients were evaluated prior to capsaicin 8% patch administration and were followed-up at 2 weeks, at 8 weeks, and at 12 weeks post administration. Visual analog scale (VAS) was used to record pain intensity and EQ-5D was used to assess the quality of life of the participants. Results: Ninety patients met our inclusion criteria (54.4% men, mean age 59.1 ± 9.2 years). At baseline the mean VAS score of the participants was 7.6 ± 0.7. A statistically significant reduction of the VAS score between baseline and week 2 (mean VAS score 5.6 ± 1.1, P < 0.001) was observed. The therapeutic effect further continued between week 2 and week 8 (mean VAS score 3.2 ± 1.2, P < 0.001) and between week 8 and at endpoint at week 12 (mean VAS score 2.6 ± 1.1, P < 0.001). Between baseline and weeks 2, 8, and 12 (end-point) a significant improvement in all 5 dimensions of EQ-5D (mobility, self-care, usual activities, pain/discomfort, and anxiety/ depression) was observed (P < 0.001) Limitations: As it is an open-label study, a prospective randomized placebo-controlled study should be designed to confirm the effectiveness of capsaicin 8% patch in patients with lumbosacral pain. Conclusions: Administration of the capsaicin 8% patch resulted in a significant relief of neuropathic pain and a significant improvement of the quality of life of patients with lumbosacral neuropathic pain. Key words: Lumbosacral pain, peripheral pain, Qutenza, neuropathic pain, capsaicin, patch, quality of life, effectiveness

The premonitory phase of migraine and migraine management

Cephalalgia ◽  
2012 ◽  
Vol 33 (13) ◽  
pp. 1117-1121 ◽  
Author(s):  
Werner J Becker
Keyword(s):  
Literature Review ◽  
Migraine Attack ◽  
Management Strategy ◽  
Controlled Study ◽  
Open Label ◽  
Double Blind ◽  
Open Label Study ◽  
Label Study ◽  
Medication Treatment ◽  
Premonitory Symptoms

Objective: The objective was to determine, through a literature review, whether treatment during the premonitory phase of migraine is a potentially useful migraine management strategy. Methods: A general literature review was done with regard to the nature of migraine premonitory symptoms, their frequency, their reliability in predicting migraine attacks, and the effectiveness of medication treatment when given during the premonitory phase. Results: Many different symptoms have been reported as premonitory symptoms that occur before migraine attacks. Up to 87% of patients with migraine may experience premonitory symptoms, although some studies have provided estimates as low as 33%. In selected patients, premonitory symptoms may be relatively reliable predictors of a migraine attack to follow. Both naratriptan (open-label study) and domperidone (double-blind, randomized, placebo-controlled study) have been reported to be effective when given during the premonitory phase. Conclusions: More research is needed, but there is some evidence that medication treatment during the premonitory phase has the potential to be helpful in selected patients with migraine.

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