4-way trial assesses non-prescription interventions, including 2 nasal sprays, for reducing seasonal respiratory illness and related antibiotic use.
Paul Little, FMedSci, Primary Care Research Centre
Image credit: University of Southampton United Kingdom
In a large scale trial of non-prescription interventions for seasonal respiratory illness, two nasal sprays were associated with shorter duration of illness and less antibiotic use compared to usual care. A behavioral intervention with a stress reduction component was also assessed, and associated with a lower incidence of illness.1 The 4-way, randomized, open-label, parallel-group trial conducted by the Primary Care Research Centre at the University of Southampton in collaboration with the University of Bristol, UK is notable for interventions that are unlikely to be tested in pharmaceutical-sponsored product trials; for recruiting and retaining a large cohort (over 13,000 randomized); and for including behavioral interventions which did not require supervised sessions.
"This is the only large, pragmatic trial of readily implementable interventions that could be widely used," Paul Little, FMedSci, Primary Care Research Centre, and colleagues indicated.
"Most previous studies of nasal sprays and behavioral interventions were small, and both the physical activity or stress reduction interventions were intensive with supervised sessions, and would be difficult to implement in primary care where resources are limited," they observed.
Little and colleagues argue that effective, low-cost, non-prescription interventions are needed to reduce the symptom burden of seasonal respiratory illness, and suggest there would also be reduction in the use of antibiotics commonly prescribed for these presentations.
Nasal sprays were chosen based on small clinical and pre-clinical studies showing that modifying the nasal environment can shorten duration of illness and/or reduce symptom severity. The two nasal sprays tested were a saline spray, thought to act as a wash to mechanically remove virus; and Vicks First Defence (Vicks UK), a gel-based product containing zinc among other ingredients that is promoted for trapping and inactivating virus.
The study found that both the saline nasal spray and Vicks First Defence gel spray significantly reduced the duration of seasonal respiratory illnesses.
The behavioral intervention, which included stress reduction and physical activity components, did not significantly reduce the duration of illness but did lower the incidence of respiratory illnesses by 5%.
The trial's design was pragmatic, reflecting real-world conditions rather than tightly controlled settings.
The inclusion of a behavioral intervention followed from studies associating stress and negative emotions with increased susceptibility to illness; and suggesting that the observed counter effect might arise from improved immune response. The fourth arm of the trial was treatment-as-usual in the primary care office, essentially brief advice on managing the illness given the day of presenting respiratory symptoms.
Participants were recruited from 332 primary care practices in the UK between Dec 12, 2020 and April 7, 2023, with 13,799 randomly assigned on 1:1:1:1 basis to the four treatment arms. The primary outcome, measured by self-report at 6 months, was total number of days of influenza, COVID-19, and/or coughs, colds, sore throat, and sinus or ear infections. Secondary outcomes included incidence of respiratory tract illnesses, possible adverse events, days of work or activity impairment, and use of antibiotics.
The nasal sprays were each provided with direction to instill 2 sprays per nostril at the first sign of an infection or after potential exposure to infection, and repeating up to 6 times per day. Participants in the behavioral intervention arm were provided access to two online modules that supported, respectively, increased physical activity, "Getting Active", and reduced stress, "Healthy Paths Through Stress." They were also provided with pedometers, which, as with the online modules, was an optional activity.
Little and colleagues reported that those using either the saline or the gel spray had statistically significantly fewer days of illness (mean 6.4 and 6.5 days, respectively) than those with treatment-as-usual (mean 8.2 days).Although the behavioral intervention group did not have significantly fewer days (mean 7.4 days), they did have a modest (5% relative reduction) in the incidence of illnesses.
Antibiotic use was lower for all interventions compared to treatment-as-usual: Incidence Rate Ratio (IRR) 0.65 (95% CI 0.50 to 0.84) with gel spray; 0.69 (0.45-0.88) with saline; and 0.74 (0.57-0.94) with the behavioral intervention.The most common adverse event was headache reported with the gel-based spray (7.8%); compared to 4.5% of those using the saline spray, 4.5% of the behavioral intervention group and 4.8% of those receiving treatment-as-usual.
The investigators acknowledged that adherence to the interventions was "modest." The nasal sprays were used at the first sign of infection by 58-60% of the assigned participants, and both with (median) twice daily dosing over a (median) course of 3 days. Little and colleagues posited that improving adherence could "plausibly" have resulted in a larger effect.
Although there was no self-report on the level of participation in the behavioral intervention, the accessing tracked by the website revealed participation by a majority of those assigned: 85.5% accessed the introductory module; 77.4% accessed the "Getting Active" module; and 50.9% accessed the "Healthy Paths".
"This was a pragmatic trial, so these are pragmatic estimates of what might happen in practice, not a tightly controlled behavioral intervention," Little told Contagion. "Worth noting, that the effect of the behavioral website was greatest for people who had both recurrent illness and comorbidity."
Little observed that the saline nasal spray appeared to be a good choice for the purpose."Saline had the same efficacy as the Vick First Defence spray and fewer side effects," he pointed out."Saline is also widely available and cheap."
Although the study is being extended to 12 months, with measures that include incidence of COVID-19, number of health service contacts, and number of days of respiratory illness and hospital admissions, Little found that this 6-month study has yielded important results.
"I think the message is that for a vulnerable group, these simple interventions work remarkably well to help manage illness, reducing severity and duration of illness, and will make an important impact on antimicrobial stewardship," Little said.
