Edinburgh and Lothian Virus Intervention Study in Kids: ELVIS Kids
Research type
Research Study
Full title
Edinburgh and Lothian Virus Intervention Study in Kids: A randomised controlled trial of hypertonic saline nose drops in children with upper respiratory tract infections(ELVIS Kids).
IRAS ID
242396
Contact name
Sandeep Ramalingam
Contact email
Sponsor organisation
University of Edinburgh
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 5 months, 31 days
Research summary
Summary of Research
Children have up to 12 viral upper respiratory tract infections (URTI) each year (otherwise known as the common cold). It isn’t practical to treat each virus individually since over 200 viruses cause URTI. Although most URTI do not result in serious problems, a number spread to the lungs resulting in more serious lower respiratory tract infections (LRTI) such as bronchiolitis or pneumonia, or trigger asthma attacks. Recently, in a clinical trial called ELVIS, we tested a way of treating URTI in adults using salt-water nasal washes and mouth gargles. Those using salt-water had significant improvement in symptoms compared to those who did not. Their symptoms didn’t last as long, they used less over-the-counter medicines, and they were less likely to pass this infection onto other family members. We also ran several laboratory experiments which showed that salt helps stop certain viruses that cause URTI multiplying by helping the body fight the viruses. Now we want to carry out a trial on children aged between 0 and 7 years old with URTI using salt-water nose drops to find out, if like in adults, their symptoms improve more quickly, they have less virus present in their nose, they pass on the cold to fewer people, and need less medical attention.Summary of Results
AIMS
Does the use of homemade hypertonic saline nose drops (i.e. salt water nose drops) in children (below 7 years of age) with the common cold reduce the duration of illness; duration & severity of individual symptoms; transmission within households; over-the-counter-medication use and wheeze?
KEY FINDINGS
In children who received hypertonic saline nose drops (HSND) [3 drops/nostril; minimum 4 times/day and up to 12 times/day, parents to adjust frequency depending on severity of symptoms], the following were significantly different compared to children receiving usual care (UC):
• Duration of illness was 2 days shorter.
• Duration of “runny nose”, “cough”, “not sleeping well”, “irritability”, “low energy” were one day shorter.
• Severity of “sore throat”, “irritability”, “feeling unwell”, “crying more”, “clinginess”, “unable to get out of bed” did not increase in those who received HSND unlike those who received usual care.
• Relative to the usual care, transmission within households was 25% lower
• Relative to the usual care, over-the-counter-medication (e.g., paracetamol, etc.) use was 31% lower.
• Rhinovirus was the most common cause of infection (73%).
• Relative to usual care, episodes of wheeze in children with rhinovirus was 75% lower.
• Duration of illness and transmission within the households were further reduced when HSND were applied within 24 hours of symptoms.
• Side effects were generally few and mild.
Most parents (82%) considered HSND beneficial and (81%) said they would use it again.WHAT DID THE STUDY INVOLVE?
• Children <7 years: randomly allocated to HSND or UC
• Parents: Taught to take nose swabs (5 consecutive days)
• HSND arm: Taught to make hypertonic saline and apply nose drops (3 drops/nostril: 4-12 times/day) until the child was well. (Salt Water Nose Drops)
• 4 times/day was the minimum. Parents were asked to increase frequency above 4 times based on severity.
• Study procedures started within 48 hours of cold symptoms
• Information was collected online, daily until the end of illness and also 28 days after the cold startedWHAT WERE THE RESULTS AND WHAT DO THEY MEAN?
Duration of illness was 2-days lower in children who received HSND compared to UC (median 6 vs 8 days, P=0.004). In the HSND arm, duration of “cough”, “runny nose”, “not sleeping well”, “irritability”, and “low energy” were a day lower compared to UC, which was significant. In the HSND arm significantly fewer children reported an increase in severity from baseline for “clinginess”, “sore throat”, “irritability”, “feeling unwell”, “crying more”, and “being unable to get out of bed”. The time to attain half the baseline severity was significantly lower in children who received HSND.Fewer children (by 11%) who received HSND reported over-the-counter-medication use (HSND: 36/144; UC: 54/150; difference: -11%, 95%CI: -21.4, -0.6; p=0.04). Fewer HSND households (by 15%) reported household members developing URTI (HSND: 66/144, UC: 92/150; difference: -15.5%, 95%CI: -26.8, -4.2; P=0.008). Transmission was significantly lower when HSND were applied ≤24 hours of symptoms starting.
A virus was identified in 75% (203/272) of samples tested. Rhinovirus was the commonest (73%, 149/203). Fewer children with rhinovirus infection who received HSND had a wheeze [HSND: 3/66; UC: 12/66; difference: -13.6%, 95%CI: -24.2, -3.1; P=0.01].
Baseline viral shedding was significantly higher in those who joined the study and therefore collected swabs ≤24 hours [mean (SD): 4.28Log10 (1.54)] compared to those who collected swabs >24 hours [mean (SD): 3.64Log10 (1.74)] of symptom onset (p=0.02). Mean viral load was lower in the HSND arm on days 2 and 3, though the differences were not statistically significant.HSND side-effects (scored 0-5) were generally mild and infrequent (sneezing: 6% (9/150) [median score 2.0, IQR (1.0-4.0)], runny nose: 19% (28/150) [median score 2.0, IQR (2.0-3.0)], and pain/soreness: 9% (14/150) [median score 0.5, IQR (0.0-2.0)]. Runny nose was expected as the solution is hypertonic, and parents were informed that the child may have some runny nose immediately after the drops. The fact that the duration of runny nose was a day lower in the HSND arm suggests that the side effect was temporary.
HSND were applied a median of 3 times/day (IQR: 2-4) for 5 days (IQR: 3-6 days). Parents reported delivering three drops/nostril per application. None in the UC arm reported using saline nose drops/sprays. Most parents (82%, 123/150) considered HSND beneficial and 81% (122/150) said they would use it again.WHAT IMPACT COULD THE FINDINGS HAVE?
• Along with the knowledge that cells produce hypochlorous acid to stop the virus from multiplying inside it and the study in adults with the common cold, we can now say “we can treat the common cold”.
• Since parents made the nose drops at home with sea salt and easily available equipment (glass jars, dropper bottles, measuring spoons, kettle) the intervention can be easily rolled out to the community. Instruction videos are at https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3t%2Fwww.elviskids.co.uk%252F.%2FNBTI%2FGv67AQ%2FAQ%2F941c64af-9bb3-4442-99df-ec6b5f98a0d5%2F2%2FhhhBg2xUOY&data=05%7C02%7Capprovals%40hra.nhs.uk%7C4470d4323bbc47d4293e08dd6302f688%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638775586601468496%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=4sqGzUBSwywJmzJBw0A2wP0zAOBmvjcj3lKxhGkD%2B5Q%3D&reserved=0 If parents are provided equipment and instructions as part of the “Baby Box Scheme”, they will be prepared for when their child has their first cold.
• The 75% reduction in wheeze in rhinovirus infected children who received HSND is promising and needs to be confirmed in a larger study as it could significantly reduce the burden on the NHS,
• As children who develop a wheeze due to rhinovirus are more likely to be diagnosed with asthma as teenagers, use of HSND in children could also reduce the burden of asthma in teenagers.HOW WILL THE OUTCOMES BE DISSEMINATED?
The results have been presented at the European Respiratory Society (Vienna), Clinical Virology Network (Birmingham) and the Royal Society for General Practitioners (Liverpool) conferences. If CSO permits, we would like to present the work in conferences areas with limited resources (Asia/Africa).
The manuscript has been submitted. Once published, the link to the publication and a summary of the results will be provided on the trial website, on the Edinburgh Clinical Trials Unit website and clinicaltrials.gov. Results will also be publicised via social media and traditional news outlets.CONCLUSION
Parent made and administered hypertonic saline nose drops is an effective intervention against the common cold in children. It reduces the duration and severity of illness. A minimum of 4 applications per day is recommended and increased by the parent up to 12 times/day based on symptom severity. Household transmission is also significantly reduced. The earlier the intervention, the better the response both in duration of illness and reduction in transmission. Wheeze following a rhinovirus infection is reduced by three fourths, which will have a significant impact on children and families. We can easily promote better child health by providing parents with glass jars, dropper bottles, measuring spoons, instructions, and sea salt as part of the Baby Box Scheme in Scotland or similar schemes across the UK. Instructions and videos are at https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3t%2Fwww.elviskids.co.uk%252F.%2FNBTI%2FGv67AQ%2FAQ%2F941c64af-9bb3-4442-99df-ec6b5f98a0d5%2F2%2FhhhBg2xUOY&data=05%7C02%7Capprovals%40hra.nhs.uk%7C4470d4323bbc47d4293e08dd6302f688%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638775586601480980%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=o%2BNQzIXVc94uycUfnX0Q5V16VmpPTXtrZzn1OejD96o%3D&reserved=0REC name
West of Scotland REC 3
REC reference
18/WS/0080
Date of REC Opinion
5 Jun 2018
REC opinion
Further Information Favourable Opinion