September 21, 2020

Background: Previous evidence has found that oseltamivir reduces median time to alleviation of influenza symptoms over placebo by about 1 day.  The benefits were greater when treatment was initiated within 24 to 48 hours of symptoms onset. Many previous trials have been criticized for under-recruiting, selective reporting of outcomes, and not including enough children/older patients. Additionally, use of oseltamivir is known to cause side effects such as headaches, nausea/vomiting and, in some cases, neuropsychiatric illness. The CDC currently recommends treatment with oseltamivir in patients with confirmed or suspected influenza who are hospitalized, severely ill, or have higher risk for influenza complications as well as consideration of treatment for symptomatic outpatients if treatment can be initiated within 48 hours.

September 17, 2020

Background: Baloxavir (trade name Xofluza) was approved for the treatment of acute, uncomplicated influenza in patients > 12 years of age in October 2018. However, high-quality data has been underwhelming at best for its efficacy in treatment. Back in November of 2018, REBEL EM concluded:

Clinical Take Home Point: Consistent with every other study on anti-viral medications for influenza, baloxavir appears to decrease duration of symptoms, especially in patients treated within 24 hours of symptoms, BUT a massive exclusion list, cost of the medication, increased resistance after initiation, results only applicable to H3N2 (88% of patients with flu), no comparison to standard care (i.e. symptom based therapy), pharma sponsored study, and no patient oriented outcomes, it is hard to make an argument for the use of baloxivir in patients with confirmed influenza. This trial should be a reminder as to why an industry funded trial, without full release of data, and cherry picked endpoints should not be used to change practice.

Continued research on effective anti-influenza drugs is critically important particularly with the potential for a “double pandemic” in the coming months. While treatment results are modest at best, baloxavir has potential as a prophylactic medication as well.

September 14, 2020

Background: Though it’s been stated numerous times on this blog, it bears repeating: the pillars of sepsis care remain early identification of sepsis, early appropriate empiric antibiotics, source control, and supportive care. The focus should be on getting the basics right but, it is important to evaluate whether other adjunctive therapies can help decrease mortality in a common and frequently fatal condition. Ascorbic acid and thiamine deficiency have been described in patients with sepsis and are thought to be due to reduced intake and increased metabolic demands.  Corticosteroids have had mixed results but seem to improve shock reversal in patients with septic shock based on best available evidence (Link is HERE). There have been a slew of RCTs evaluating this metabolic cocktail (vitamin C, thiamine, & corticosteroids) in recent months. Though biologically plausible, this treatment approach has not been shown to improve patient-oriented outcomes.

September 10, 2020

Background: There are three randomized clinical trials now published on remdesivir in the treatment of COVID-19 pneumonia (RCT 1, RCT 2, & RCT 3). The 1st trial, performed in China, was terminated early due the lack of patients to enroll and, as a result, did not give strong recommendations.  The 2nd trial (ACTT-1) showed a statistically significant 4-day reduction in time to recovery. However, it was also terminated early due to an interim analysis, which meant we do not have outcomes on 30% of patients enrolled.  Finally, the 3rd RCT compared a 5-day to a 10-day course of remdesivir and showed no difference in outcomes with more acute kidney injury in the 10-day course. All of these trials have significant issues leaving clinicians unsure of the efficacy of the drug, when to administer it, how long to give it for and, in which patient group it should be given. We now have our 4th RCT of remdesivir evaluating the efficacy and adverse events of remdesivir administered for 5- or 10-days vs standard care in hospitalized patients with moderate COVID-19.

September 5, 2020

Background: Over the past few years, corticosteroids have gained traction in the treatment of patients with ARDS and septic shock.  Trials such as APROCCHSS and ADRENAL have shown that the use of corticosteroids is associated with more rapid resolution of shock, weaning from mechanical ventilation in septic shock, and, potentially lower mortality. The RECOVERY trial, the largest RCT to date on the use of corticosteroids in COVID-19, showed treatment with dexamethasone (6mg/d for 10 days)  had an absolute mortality reduction of 11% in patients receiving mechanical ventilation   (IMV) (NNT = 9), 3.5% decreased mortality in patients requiring O2 but not IMV (NNT = 29) and an overall mortality reduction 3% (NNT = 3) compared to usual care alone.  However, there was a signal toward harm (not statistically significant) in patients not receiving respiratory support. In the September 2020 issue of JAMA, there were 3 RCTs (REMAP-CAP, CoDEX, & CAPE COVID) assessing corticosteroid therapy in critically ill patients with COVID-19, as well as a prospective meta-analysis. All 3 RCTs halted enrollment in June 2020 after the RECOVERY trial press release.  The prospective meta-analysis from the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) working group pooled data from 7 trials (RECOVERY, REMAP-CAP, CoDEX, CAPE COVID, and 3 additional trials) with roughly 1700 patients. In this post we will review the REMAP-CAP, CoDEX, and CAPE COVID trials, as well as the prospective meta-analysis.
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