In the article titled “Safety of hydroxychloroquine among outpatient clinical trial participants for COVID-19”, Lofgren et al. conducted clinical trials to ascertain the safety of hydroxychloroquine. In the wake of COVID-19, Lofgren et al. set out to test the safety of hydroxychloroquine among outpatients. The use of hydroxychloroquine for inpatients and outpatients with COVID-19 showed an increased risk for cardiac side effects, causing the US Food and Drug Administration (FDA) to warn against the use of the drug outside of hospital settings (Lofgren et al., 2020). The drug led to QT prolongation, especially when used alongside azithromycin or in patients with kidney and heart problems history. The research aimed to establish the safety of hydroxychloroquine in the management of COVID-19. The researchers aimed at eliminating the fears evoked by its use in hospitalized patients with comorbidities and are under several other medications. Since the drug has a clean safety record of over 65 years, reaffirming its safety is critical in the management of the pandemic (Lofgren et al., 2020). Hence, the significance of the study is to find out how safe it is to administer hydroxychloroquine to COVID-19 patients.
The study included three randomized, placebo-controlled, and double-blind trials to investigate hydroxychloroquine as pre-exposure and post-exposure prophylaxis and early treatment of the coronavirus. During the first two trials, the scientists investigated preemptive early treatment (PET) and post-exposure prophylaxis (PEP), while pre-exposure prophylaxis (PREP) was tested in the third trial (Lofgren et al., 2020). Randomized trials using the drug and placebo are the most effective in clinical tests. The study included 2795 participants enrolled through an online survey from across the United States and a few Canadian provinces. Only 2544 (N = 2544) participants completed the survey, the rest failing to follow up (Lofgren et al., 2020). Therefore, the dropout rate from the study is equal to 0.09%. Although the percentage is small, researchers did not follow up to know whether the participants experienced adverse effects from the drug and hence, stopped responding.
The instrument employed was an online survey that participants filled on days 1, 3, 5, 10, and 14 to report their side effects, new symptoms, drug adherence, COVID-19 testing, and hospitalization (Lofgren et al., 2020). Participants in the PREP trial reported weekly on these same items. The self-reporting feature of the instrument provides advantages and disadvantages to the study. For example, patients may lack insight into their medical condition, including drug side effects and symptoms. More specifically, the symptoms of COVID-19 are a little difficult to tell, and the widespread panicky situation of the pandemic might create false symptoms. Therefore, self-reported surveys for clinical trials are relevant, but their reliability is adversely affected by various factors mentioned above.
Statistical analysis involved summaries of the frequency of the survey items, including side effects and other drug-related adverse events, such as deaths, other life-threatening occurrences, and hospitalizations. The researcher used an interquartile range for the participants’ demographics. The chi-square test was conducted on the participants who received medication, N = 1312, to produce the p-values for various events (Lofgren et al., 2020). A similar statistical test was carried out on groups of participants to produce their respective p-values. The statistical methods were relevant because frequency is the most important measure in clinical trials. P-values are important in distinguishing between events caused by the drug and ones that could have occurred by chance.
All the participants were adults aged 18 years and above. Other exclusion criteria included being under 40 kg in weight and being pregnant or breastfeeding. Therefore, participants were both men and women aged 18 years and above. Ethnically, most of the participants were whites or Caucasians, followed by Asian and Hispanic. Additionally, 51.4% were women, while 74.4% were healthcare workers or first responders (Lofgren et al., 2020). Considering that majority of the participants had medical and drug knowledge, their self-reporting reliability is higher than that of the ordinary respondents. In addition, the study included all adult age groups, major ethnicities, and both genders. Therefore, the findings are generalizable to a population with similar characteristics.
Outcomes of the clinical trials manifested side effects, including stomach upset, nausea, vomiting, diarrhea, gastrointestinal symptoms, and neurologic reactions in 29% of the PEP and PET trials (Lofgren et al., 2020). Although sudden cardiac death and arrhythmias were not reported, seven allergic reactions were noted. Four percent of the PET and PEP participants stopped medications due to adverse side effects. Since gastrointestinal effects are an effect of COVID-19, researchers used chi-square to determine statistical significance between the placebo and the hydroxychloroquine group. Nausea or stomach upset reports between the two groups had no statistical significance difference as p =.12, which is greater than the recommended p ≤.05 (Lofgren et al., 2020). Similarly, for vomiting, diarrhea, and abdominal pains, with p =.14. In the three trials, 1% were hospitalized, and three deaths were reported (Lofgren et al., 2020). Researchers concluded that hydroxychloroquine is safe for use among COVID-19 outpatients but should not be paired with azithromycin. They also warned against high dosages for hospitalized patients, citing the possibility of cardiac complications.
The researchers achieved high degrees of reliability and validity by achieving over 90% participation from respondents. However, those that dropped out were not followed up to discover their reasons for opting out. The biases of self-reporting were a threat to the research, but it is lessened by having the majority of participants being health workers who understand symptoms, side effects, and allergies. The researchers also used randomized sampling to recruit the sample, ensuring reliability.
The strengths of the study include a large sample size of 2544 participants and innovative clinical trial designs. By sampling such a huge number across two countries, the researchers ensured the inclusion of many varying demographical factors. Nevertheless, the use of social media and the Internet for recruitment is a limitation because older participants could not be recruited. This explains why the median age of the participants is 40 years (Lofgren et al., 2020). In addition, the study did not include hospitalized patients who are more likely to suffer cardiac-related side effects than healthier outpatients. Future studies must involve large-scale and continuous clinical trials to ascertain the drug’s safety. Trials on older patients with comorbidities can also produce specific results for the age group.
Nurse practitioners (NP) can prescribe drugs to patients and are responsible for ensuring that patients have proper medications in the right dose. In addition, NPS must notice any adverse side effects of any prescribed drugs and act quickly to ensure the patients get help. Since hospitals have seen increased patient numbers and health worker shortages during the pandemic, NPs must understand the drugs used for the treatment of COVID-19. This research contributes to the knowledge about hydroxychloroquine usage for outpatients with the virus.
Overall, NPs must understand how drugs interact and their side effects on patients. In the article, the researchers used online surveys to collect data from participants spread across two countries. The Chi-square method was employed to produce statistical significance values for the control group and the medicated group. The study’s limitation emerges from the use of internet-based recruitment tools and the exclusion of hospitalized COVID-19 patients.
Reference
Lofgren, S. M., Nicol, M. R., Bangdiwala, A. S., Pastick, K. A., Okafor, E. C., Skipper, C. P.,… & Rajasingham, R. (2020). Safety of hydroxychloroquine among outpatient clinical trial participants for COVID-19. In Open forum infectious diseases (Vol. 7, No. 11, p. ofaa500). US: Oxford University Press.