Hypertonic Saline Nasal Irrigation and Gargling for the Common Cold.
Hypertonic Saline Nasal Irrigation and Gargling for the Common Cold.
Viral upper respiratory tract infections (URTI), one of the commonest infection faced by
 humans, have a significant impact on individuals, families, health service and economy.
 Though rhinoviruses are called the "common cold virus", numerous viruses can cause URTI.
 Hence virus specific remedy for URTI is impractical. There are currently no evidence-based
 interventions that reduce the severity, symptom duration or viral shedding. Preliminary
 evidence suggests that hypertonic saline nasal irrigation and gargling (HSNIG) may reduce the
 duration of symptoms.

 With this pilot randomised controlled trial (RCT), the investigators aim to assess the
 feasibility of undertaking a definitive RCT of HSNIG in adults with URTI. This pilot focuses
 on recruitment rate, willingness to be randomised, acceptability, compliance and likely
 effect size of the intervention.

 This pilot RCT compares HSNIG vs. usual care in 60 adults. Serial self-collected
 mid-turbinate swabs will help assess change in viral shedding. Symptomatic relief is measured
 by a validated symptom score. A questionnaire based participant feedback will help assess
 intervention and trial procedures.

 This mixed-methods pilot trial will help inform plans for a definitive RCT of this low-cost
 intervention that has the potential of substantial health and societal benefits.
1. Aims:

 To assess the feasibility of undertaking a RCT of HSNIG in adults with URTI focusing on
 recruitment rate, willingness to be randomised, acceptability, compliance and likely
 effect size of the intervention.

 1.1. Research questions:

 1. What is the likely rate of recruitment and loss to follow-up?

 2. Are the study procedures acceptable to participants?

 3. Is there a likely reduction in duration of symptoms and viral shedding?

 4. What effect size is estimated for the definitive trial in relation to duration of
 symptoms and improvement in quality-of-life?

 2. Subjects:

 2.1 Sample size: This is a pilot trial so no formal sample size calculations are
 indicated. However, with a sample size of 27 per group the investigators would be able
 to express the proportion of those who return the symptom score diary and samples within
 that group to within ±19% based on a two-sided 95% confidence interval around an
 expected proportion of 0.5. With the two groups combined [i.e. a sample size of 54] the
 investigators would be able to express a proportion to within ±13%. To allow for 10%
 dropouts the sample size has been increased to 30 per group.

 2.2 Recruitment: The investigators propose to enrol a total of 60 participants (30/arm)
 for this pilot. The investigators plan to recruit by advertising the study in the
 community by the following routes.

 -  Sending flyers to parents through schools run by Edinburgh and Midlothian councils.

 -  Study website (www.elvisstudy.com), National Health Service (NHS) Lothian,
 University of Edinburgh websites.

 -  Local media coverage by way of interviews.

 -  Flyers in workplaces with large numbers of staff (e.g. banks, supermarkets,
 councils).

 -  Posters in pharmacies and General practitioner (GP) surgeries.

 Interested individuals will be asked to contact the trial nurse at the clinical research
 facility (CRF) situated at the Royal Infirmary of Edinburgh (RIE) and Western General
 Hospital within 48 hours of symptom onset. The trial nurse will consent, randomise, and
 recruit volunteers. Participants will be advised to go to their GP as per norm if they
 become unwell and that they can withdraw from the study if they so wish for other
 reasons. At the end of their participation in the study, they will be given £30 as
 recompense for any inconvenience.

 3. Research Methods:

 3.1 Randomisation: Participants are randomised in a 1:1 ratio to receive intervention or
 control, this has been done using an online randomisation minimised by sex (M/F) and
 smoking status (current/not a current smoker) and allocated to each treatment arm with a
 probability 0.9 to ensure a random allocation.

 3.2 Instructions to participants: 3.2.1 Both arms: Participants are taught to complete
 (online or paper) a modified short Wisconsin upper respiratory symptom survey
 (WURSS-21-Scot) and the EQ-5D-5L questionnaire. Baseline symptom scores are recorded by
 the participant.

 Participants are taught to collect nasal swabs. A baseline swab is collected under
 observation and sent to the virology laboratory at the Royal Infirmary of Edinburgh
 (RIE). Swabs, transport medium and Royal Mail Safebox will be provided to the
 participant to collect a nasal swab first thing in the morning (before HSNIG for the
 intervention arm) for four consecutive days and return to the laboratory.

 3.2.2 Intervention arm: The intervention group will be shown a video on preparing the
 hypertonic sea-salt solution and how to perform HSNIG. They will be asked to perform the
 procedure under supervision. The trial nurse will help them identify the highest
 concentration of saline they are comfortable with. Participants are advised to perform
 the intervention as frequently as required (expected frequency around 6 times/day for
 the first two days, reducing in frequency from day 3 as symptoms improve). A package
 containing instructions, digital-measuring spoon, sea-salt, and equipment for irrigation
 and flask (if they wish to prepare solution for multiple uses during the day) will then
 be handed over to the participant. Participants in the intervention arm will also
 document compliance and side effects daily

 3.2.3 Control arm: They are advised to manage the URTI as they normally do.

 3.3 Data collection: 3.3.1 "WURSS-21-Scot" diary and EQ-5D-5L Questionnaire: All
 participants will complete the "WURSS-21-Scot" diary at a set time during the day.
 Participants will answer the question "how unwell do you feel today". If they score >0,
 then symptoms and functional ability are graded 0-7. They then answer the global change
 question. Total score/day is calculated by summing the scores of all 10 symptoms daily.
 All participants will also answer the EQ-5D-5L questionnaire.

 The following information is collected at recruitment: where they heard about the study,
 influenza vaccination history, number of family members and whether sufficient
 information was provided.

 The intervention arm will also answer the following questions daily: how many times they
 performed HSNIG, if they performed one or both parts of HSNIG and if there were any side
 effects.

 Both arms will answer if they had to take any medications for the URTI and whether they
 needed to contact the GP for further management of their URTI.

 Diaries are maintained until participant records "not unwell" on two consecutive days or
 for a maximum of 14 days or until follow up is terminated because the individual needs
 further treatment.

 3.3.2 Virology: Swabs will be sent to the Department of Virology, RIE for testing.
 Baseline samples will be tested to identify individuals in whom an aetiology can be
 proven. If a viral aetiology is identified, all samples (day 0 - day 4) will be tested
 in parallel to identify change in viral shedding.

 3.3.3 Data collection procedures: The trial nurse will follow up participants who do not
 complete the diary or return samples (after 48 hours of expected return). Information on
 number of family members with URTI will be collected at the end of the study. Feedback
 will be collected from participants after the follow-up period. These will address
 acceptability, health service use, costs to the patient and suggestions for improving
 the study procedures for the main trial.

 4. Data Analysis:

 The number of participants returning swabs, completing diaries and following treatment as per
 protocol will be presented as percentages (with 95% confidence intervals). The investigators
 will present recruitment as an overall rate, but also graphically as there is likely to be
 seasonal variation. Using results from the swabs the investigators will determine when a
 person stops viral shedding and, using chi-square and chi-square test for trend, determine if
 there is a relationship between groups. Using two-sample t-tests or non-parametric equivalent
 as appropriate the investigators will determine if there is any evidence of a difference in
 the duration of symptoms and symptom severity [as defined by the maximum WURSS-21-Scot score
 over treatment period]. Feedback will be analysed using a conventional content analysis
 approach, with emerging findings discussed by the research team to aid interpretation of
 findings.
Inclusion Criteria:

 -  Clinical diagnosis of upper respiratory tract infection (URTI)

 -  Within 48 hours of onset

 Exclusion Criteria:

 -  Onset of URTI >48 hours

 -  On antibiotics

 -  Pregnancy

 -  History of chronic illness or immunosuppression

 -  Allergic rhinitis

 -  Unable to perform nasal irrigation and gargling

 -  Taking part in another medical trial