Efficacy of Outpatient Treatment with Ciclesonide in COVID-19
Systemic corticosteroids have been used to treat severe COVID-19 infection, resulting in lower 28-day mortality rates in these patients. But the role of inhaled steroids in mild to moderate COVID-19 infection is less clear. Inhaled ciclesonide is a promising candidate: it’s been shown to have anti-inflammatory properties in lung and bronchial structures through inhibition of the PAK1 enzyme in cells, a known pathogenic pathway for COVID-19.
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A phase 3, multicenter, double-blind, randomized clinical trial conducted in 400 nonhospitalized patients with mild to moderate COVID-19 infection from June to November 2020 compared inhaled ciclesonide to placebo. Patients were randomly assigned to receive ciclesonide (n = 197) by metered-dose inhaler, 160 mcg/actuation, 2 actuations b.i.d., for a total daily dose of 640 mcg, or placebo (N = 203) for 30 days. The primary endpoint was time to alleviation of COVID-19-related symptoms, including cough, dyspnea, fever, shaking chills, muscle pains, headache, sore throat, and lack of sense of taste or smell). The study also followed the patients to determine if they had subsequent emergency department (ED) visits or hospital admissions for reasons attributable to COVID-19. Patients were eligible for the study if they were older than age 12, were positive for SARS-Cov2 but not at risk for hospitalization, with an oxygen saturation of at least 93% on room air and at least one of the common symptoms of COVID-19 infection. They were told to notify researchers if they experienced an ED visit or hospitalization during the study; they were instructed to seek ED evaluation if their oxygen saturation level fell below 92%. All patients took the study medication for 30 days, even if symptoms resolved earlier.
The median time to alleviation of all COVID-related symptoms was 19.0 days in both the ciclesonide and placebo arms. There was also no difference in resolution of symptoms by day 30 (odds ratio, 1.28). The most common symptoms on day 30 were cough (11.7% vs. 12.3%), muscle pain (9.6% vs. 8.9%), and dyspnea (10.2% vs. 7.9%). But though there were no differences in resolution of symptoms, those treated with inhaled ciclesonide had fewer subsequent ED visits or hospital admissions for reasons related to COVID-19 by day 30 compared to those receiving placebo (1.0% vs. 5.4%; odds ratio, 0.18).
An important consideration is that it’s not uncommon for patients with COVID-19 infection to continue to experience lingering symptoms for some time; as a result, testing for this endpoint may have masked a significant portion of the population who were able to safely return to usual life and who were no longer at risk for viral transmission. The secondary outcome of fewer ED visits or hospitalizations may be more relevant, offering evidence that inhaled ciclesonide or other steroids are a low-cost intervention that can prevent such events. (Clemency, B. M., et al. (2021). Efficacy of inhaled ciclesonide for outpatient treatment of adolescents and adults with symptomatic COVID-19: A randomized clinical trial. JAMA Intern Med, 182(1), 42–49. Retrieved February 2022 from https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2786012)
Released: February 2022
Nursing Drug Handbook
© 2022 Wolters Kluwer
Which Vaccine for COVID-19 Booster?
Although the vaccines against SARS-CoV2 that have been available in the United States since early 2021 provide high levels of protection against severe illness and death resulting from COVID-19 infection, the increasing number of breakthrough infections in fully vaccinated persons from the delta variant starting in late spring 2021, followed by the even more transmissible omicron variant, raised concerns about waning immunity. The phase 1-2, open-label MixNMatch study, conducted at 10 sites in the United States, was designed to assist in the development of booster strategies during the ongoing pandemic. It assessed both homologous boosters (the same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in persons who had completed a COVID-19 vaccination regimen at least 12 weeks earlier and had no reported history of SARS-CoV2 infection.
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MixNMatch enrolled 458 people, who received a booster from one of three vaccines: 154 received the Moderna mRNA vaccine, 100 mcg; 150 received the Johnson & Johnson/Janssen vaccine, 5 × 1010 virus particles; and 150 received the Pfizer/BioNtech vaccine, 30 mcg. Both homologous and heterologous booster vaccines had an acceptable safety profile and immunogenicity. As with the primary series of vaccines, mild adverse effects—myalgia, headache, malaise, injection-site pain—were common. Reactogenicity was similar to that seen in previous evaluations of the vaccines and didn’t differ between homologous and heterologous boosters. In addition, all boosters were immunogenic in participants, regardless of which primary vaccine regimen they had received.
The factor increases after booster in both binding and neutralizing antibody titers were similar or greater after heterologous boosters than after homologous boosters. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20; in heterologous boosters, they increased by a factor of 5 to 55. Increases were greatest in participants who received an mRNA booster after a primary J&J/Janssen vaccination (34 with Pfizer/BioNTech, 55 with Moderna). Interestingly, binding antibody titers peaked at day 15 for those who received an mRNA vaccine as a booster and were similar or declining on day 29; for those who received the J&J/Janssen vaccine as a booster, titers on day 29 were similar to those measured on day 15.
Spike-specific T-cell responses increased in all combinations but the homologous J&J/Janssen-boosted subgroup. CD8+ T-cell levels were more durable in participants whose primary vaccine was J&J/Janssen, and heterologous booster with that vaccine substantially increased spike-specific CD8+ T-cells in those who had previously received the mRNA vaccines. These vaccine-elicited spike-specific T-cell responses may contribute to the antibody response and the prevention of severe disease in cases of breakthrough infections.
These data strongly suggest that both homologous and heterologous booster vaccine doses will increase protective efficacy against symptomatic SARS-CoV2 infection. The data show that an immune response will be generated for each of these vaccines used as a booster regardless of the primary vaccination regimen. (Atmar, R. L., et al. (2022). Homologous and heterologous covid-19 booster vaccinations. New Engl J Med. Retrieved February 2022 from https://www.nejm.org/doi/full/10.1056/NEJMoa2116414?query=TOC)
Released: February 2022
Nursing Drug Handbook
© 2022 Wolters Kluwer
Oral Penicillin Recommended for Treatment of High-Risk Rheumatic Heart Disease
More than 39 million people worldwide have rheumatic heart disease, a condition in which heart valves are permanently damaged as a result of a bout of rheumatic fever, which can occur if strep throat or scarlet fever is inadequately treated. Most cases of rheumatic heart disease, especially in lower income nations, aren’t diagnosed until after severe valvular heart disease or other CV complications have already developed.
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The recommended treatment for rheumatic heart disease is a long-term (that is, 10 years or longer) regimen of penicillin G benzathine, given by IM injection every 3 to 4 weeks. For many years, death after these injections were ascribed to anaphylaxis, but evidence is growing that points to a different cause: cardiac compromise. Such a shift in perspective has important ramifications for the management of this disease, and an American Heart Association Presidential Advisory statement addresses this, recommending oral penicillin as a safer option for some patients with rheumatic heart disease at high risk for a vasovagal response and resultant cardiac compromise.
The advisory panel divided patients into low-risk and elevated-risk groups, based on symptoms and the severity of the underlying valvular heart disease. The risks of cardiac compromise are highest among patients with severe valvular disease, as they have low CV reserves and may not compensate well to pain on injection. Patients with severe mitral stenosis, who depend on increased preload to maintain cardiac output, are at highest risk.
The advisory panel suggests that those with a low risk of cardiac compromise and no history of penicillin allergy or anaphylaxis can safely continue to receive the injectable penicillin G benzathine, and they advocate a multifaceted strategy for vasovagal reaction risk reduction in those patients. Noting that pain or fear of the penicillin injection, along with physiologic and other stresses, such as dehydration, drives the vasovagal response, the advisory panel recommends the following protocols:
- Reduce injection pain and anxiety by applying pressure and ice to the injection site and administering acetaminophen or NSAIDs.
- Ensure that patients are well-hydrated and have eaten a small amount of food in the hour before injection.
- To reduce the risk of postural hypotension and fainting, administer the injection with the patient supine.
- Ensure that those administering the injection can recognize and quickly treat any cardiac symptoms.
For those in the elevated-risk group, the advisory panel states that treatment with oral penicillin should be strongly considered. They note that making a change from injectable to oral penicillin prophylaxis carries its own challenges, particularly requiring a commitment from governments to ensure its availability and from health care providers to educate patients. (American Heart Association. (2022). Oral penicillin, not injectable, advised for people with high-risk rheumatic heart disease. Retrieved February 2022 from https://newsroom.heart.org/news/oral-penicillin-not-injectable-advised-for-people-with-high-risk-rheumatic-heart-disease?preview=326b; Sanyahumbi, A., et al. (2022). Penicillin reactions in patients with severe rheumatic heart disease: A Presidential Advisory from the American Heart Association. J Am Heart Assoc. Retrieved February 2022 from https://www.ahajournals.org/doi/10.1161/JAHA.121.024517)
Released: February 2022
Nursing Drug Handbook
© 2022 Wolters Kluwer
Inhaled Treprostinil Continues to Prevent Progression Events in Pulmonary Hypertension on Post Hoc Analysis
Interstitial lung disease complicated by pulmonary hypertension (PH-ILD) results in worse outcomes than other forms of ILD: worsened functional status, increased requirements for supplemental oxygen, increased health care resource use, and increased mortality. INCREASE, a 16-week, phase 3, multicenter, double-blind, placebo-controlled study, showed a benefit from inhaled treprostinil, a stable prostacyclin analogue with potent vasodilation on pulmonary vasculature, in patients with PH-ILD. The study’s primary endpoint—change in 6-minute walking distance from baseline, a measure of exercise tolerance—showed improvement of 31 meters in the active treatment group. In addition, treatment with inhaled treprostinil resulted in a delayed time to first disease progression compared to placebo, and fewer clinical worsening events.
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Post hoc analysis sought to determine the efficacy of continuing inhaled treprostinil use after disease progression. It therefore evaluated the effects of continued treatment on the frequency of multiple disease progression events. On analysis, 147 disease progression events occurred in the inhaled treprostinil group (in 89 of 163 patients; 55%) compared with 215 events in the placebo group (in 109 of 163 patients; 67%). The incidence of each type of disease progression event was also lower in the inhaled treprostinil group vs. placebo:
- 15% decline in 6-minute walking distance (45 vs. 64 events)
- exacerbation of lung disease (48 vs. 72 events)
- 10% decline in forced vital capacity (19 vs. 33 events)
- cardiopulmonary hospitalization (23 vs. 33 events)
- death (10 vs. 12 events).
Fewer patients receiving inhaled treprostinil experienced multiple progression events compared with those receiving the placebo (35 patients, 22% vs. 58 patients, 36%).
This comprehensive analysis of all disease progression events in the INCREASE study provides a more complete view of the benefits of inhaled treprostinil in patients with PH-ILD and supports the continuation of this therapy in those patients who do experience a clinical worsening event. (Nathan, S. D., et al. (2021). Efficacy of inhaled treprostinil on multiple disease progression events in patients with pulmonary hypertension due to parenchymal lung disease in the INCREASE trial. Am J Respir Crit Care Med, 205(2), 198–207. Retrieved February 2022 from https://www.atsjournals.org/doi/full/10.1164/rccm.202107-1766OC; Behr, J. (2022). Inhaled treprostinil in pulmonary hypertension in the context of interstitial lung disease: A success, finally. Am J Respir Crit Care Med, 205(2), 144–145. Retrieved February 2022 from https://www.atsjournals.org/doi/full/10.1164/rccm.202110-2444ED)
Released: February 2022
Nursing Drug Handbook
© 2022 Wolters Kluwer