Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05104372 |
| Other study ID # |
16/136/109-AAIP-NW |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2021 |
| Est. completion date |
November 30, 2021 |
Study information
| Verified date |
November 2021 |
| Source |
The Allergy and Asthma Institute, Pakistan |
| Contact |
OSMAN M YUSUF, MBBS, PhD |
| Phone |
+923008552557 |
| Email |
allergypk[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Nasal washing (washout) followed by gargles with hypertonic saline (HSNIG) is believed to be
effective in reducing the duration of illness in those with clinically suspected or confirmed
COVID-19 being managed at home, and also is effective in reducing complications of COVID-19
and onward household transmission.
This study plans to investigate whether the use of HSNIG performed by adults with symptoms
consistent with COVID-19 reduces the duration of symptoms when compared to participants
managed using standard care.
Description:
BACKGROUND
Analysis of data from the recent "Edinburgh and Lothians Viral Intervention Study" (ELVIS)
pilot randomized controlled trial (RCT) indicates that hypertonic saline nasal irrigation and
gargling (HSNIG) reduced the duration of coronavirus upper respiratory tract infection (URTI)
by an average of two-and-a-half days. As such, it may offer a potentially safe, effective and
scalable intervention in those with Coronavirus Disease-19 (COVID-19) following infection
with the beta-coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
The researchers recently reported that epithelial cells mount an antiviral effect by
producing hypochlorous acid (HOCl) from chloride ions. HOCl is the active ingredient in
bleach. Epithelial cells have this innate antiviral immune mechanism to clear viral
infections. Since bleach is effective against all virus types, it was tested to see whether a
range of DNA, RNA, enveloped and non-enveloped viruses were inhibited in the presence of
chloride ions supplied via salt (NaCl). All the viruses tested were inhibited in the presence
of NaCl. The human viruses which were tested included: DNA/enveloped: herpes simplex virus;
RNA/enveloped: human coronavirus 229E (HCoV-229E), respiratory syncytial virus, influenza A
virus; and RNA/non-enveloped: coxsackievirus B3.
In COVID-19, high titers of SARS-CoV-2 are detectable in the upper respiratory tract of
asymptomatic and symptomatic individuals. The titers are higher in the nose than the throat
suggesting measures that control the infection and viral shedding will help reduce
transmission.
Till the time a significant proportion of the world population is vaccinated against
COVID-19, a safe and effective intervention is needed that can be implemented globally. The
in-vitro data gives the evidence that NaCl has an antiviral effect that works across viral
types. The findings from this post-hoc analysis of ELVIS need to be interpreted with caution.
These data do however suggest that HSNIG may have a role to play in reducing symptoms and
duration of illness in COVID-19.
HYPOTHESES Primary: HSNIG is effective in reducing the duration of illness in those with
clinically suspected or confirmed COVID-19 being managed at home.
Secondary: HSNIG is effective in reducing complications of COVID-19 and onward household
transmission.
INTERVENTION The Intervention group will be suspected or confirmed COVID-19 infected
individuals. They will make hypertonic saline at home, and perform nasal washing and gargles,
as per instructions and study videos, which will be available to be viewed by the
intervention group only, in the study website "www.nasalwash.pk". This will be used as
required to a maximum of 12 times/day for a maximum of 14 days. Participants are informed
that symptoms might reduce after HSNIG, but may return after a while. Symptoms could hence
return as early as 30 minutes to many hours after HSNIG. Participants will be advised to
perform HSNIG as soon as symptoms return, and as many times as needed (but not more than 12
times/day) until they become symptom-free, or until the end of their study participation
(either on day 14, or on admission to hospital or on withdrawal from the study), and follow
standard advice from their physicians or the Pakistan Government website on personal and
household hygiene and social distancing: http://www.covid.gov.pk/prevention.
CONTROL The participants randomized to the control arm will be asked to perform ablution,
which includes washing of the nose by the prescribed Islamic method with plain water,
(instructions and study videos are available to be viewed by the control group in the study
website) and to follow the guidance on personal and household hygiene and social distancing
as advised by the Ministry of Health, Government of Pakistan, at
http://www.covid.gov.pk/prevention.
OBJECTIVES Primary Objective To investigate whether the use of HSNIG performed by adults with
symptoms consistent with COVID-19 reduces the duration of symptoms when compared to
participants managed using standard care.
Secondary Objectives
To determine the effect of HSNIG on:
1. Severity of all symptoms
2. Duration and severity of individual symptoms
3. Over-the-counter medication use
4. Contact with primary care, or Covid19 emergency helpline.
5. Hospital emergency attendance and/or hospital admission, and diagnosis
6. Number of household contacts infected
7. Side-effect of HSNIG.
ENDPOINTS Primary Endpoint Self-reported time to resolution as assessed by completion of the
validated self-reported UK-adapted short form of the Wisconsin Upper Respiratory Symptom
Survey (WURSS-24) which will be used to collect daily symptom data.
Secondary Endpoints
1. Severity of all symptoms
2. The length of time for individual symptoms to resolve
3. Severity of individual symptoms
4. Contacting healthcare.
5. Participants needing physician appointments.
6. Participants attending hospital
7. Length of stay in hospital, if admitted
8. Number of participants reporting over the counter medication use
9. Reduction in transmission to household contacts
10. Number of participants reporting side effects of nasal irrigation
11. Types and severity of side effects reported
STUDY DESIGN
This study is a pragmatic, non-CTIMP, web-based, Bayesian adaptive randomized controlled
trial (RCT) of HSNIG vs. standard care in adults over 18 years of age with suspected or
confirmed COVID-19. The study will run throughout the course of the COVID-19 pandemic until
numbers have been recruited for sufficient analysis, or until 30th of November 2021.
Participants are recruited within 5 days of developing COVID-19 symptoms by use of the study
website ("www.nasalwash.pk"), study advertising through traditional media such as radio and
internet advertisements, as well as social media. Paper leaflets will be distributed at
chemists, doctors' clinics, COVID testing centers, and through organizations working with
COVID patients. For the purposes of this study, symptoms or diagnosis of COVID-19 are defined
as at least one of the following symptoms, which include:
- Respiratory symptoms, such as cough and shortness of breath
- Fever
- Muscle pain
- Headache
- Sore throat
- New loss of taste or smell
- Severe fatigue
- Nausea or vomiting
- Diarrhea
- Congestion or runny nose
Willing participants will be directed by the study advertising to a study specific webpage at
"www.nasalwash.pk", where they will be able to access further study information and
documents, which will include a Patient Information Sheet and a Consent form. All data
including consent will be obtained electronically, details of how the process of electronic
consent will work is given in detail below in the section titled "Consenting Participants".
After obtaining their electronic consent, they will be randomized automatically by the
software to either the Intervention Group, or the Control Group. They will be provided a
password to a personal area, which will contain an instructional video on whether they will
perform hypertonic saline nasal irrigation and gargles (the intervention group); or do either
nothing, or regularly continue to perform ablution for prayers (the control group). The
affected individual (not more than one participant per household) will be centrally
randomized through an easy to access web-based randomization schedule hosted at the study
data center at the Allergy & Asthma Institute, Pakistan, in collaboration with the Edinburgh
Clinical Trials Unit, University of Edinburgh.
All pre- and post-randomization data will be collected through mobile phone/web-based
questionnaires (see Daily Study Diary, Daily Symptom report, End of Illness questionnaire and
Day 14 questionnaire). Participants will be randomized to either a Control arm of standard
symptomatic care, or an Intervention arm of HSNIG up to 12 times per day for a maximum of 14
days or until asymptomatic, alongside standard symptomatic care. All participants will be
required to complete a daily symptom diary until Day 14 and all participant will be asked to
complete the Day 14 questionnaire, which will establish if any other members of the
participant's household have developed symptoms of COVID-19. If a participant's symptoms
clear before Day 14, they will be invited to complete the End of Illness questionnaire
(healthcare use, adverse events, acceptability, infection in household contacts) on the day
that these symptoms resolve, and continue to fill in the Daily Diary, in case of recurrence
of symptoms until Day 14.
Participants who have been randomized to the Intervention arm, will be directed towards a
password-protected webpage featuring videos and instructions on how to prepare the hypotonic
saline solution and how to perform HSNIG, while those randomized to the Control arm will be
directed towards a password-protected webpage featuring a video and instructions on how to
perform ablution with plain water and gargling, as well as washing the nose other than
ablution, but with plain (salt-free) clean water.
The patients who have been randomized to the intervention arm will be directed to the
instructional video in which it will be explained that they should take 250 ml of clean water
(water which has been boiled and cooled, or filtered or mineral water) in the measuring jug
provided, and add one level teaspoon of salt (6.5 grams) and use this salty water for nasal
washing and gargles. In order to standardize the study, and since sea-salt is not very
commonly available in Pakistan, patients in the intervention arm will be provided sea salt
(or preservative-free sodium chloride) for the treatment by the project, along with a
measuring spoon calibrated at 6.5 grams of salt when filled level, and a graduated container
showing 250 ml. This will be posted to them by courier as soon as they are randomized into
the trial / intervention arm of the study. The addition of 6.5 grams of salt to 250 ml of
water will make a 2.6% saline solution.
At consent, participants will be given the option to consent to the future collection of
samples for COVID-19 serological analysis.
It is also proposed to randomly select approximately a proportion of all participants,
according to availability of funds for testing for SARS-CoV-2 infection by RT-PCR, which will
include a swab sample from the nose and/or the throat. to support the diagnosis of COVID-19.
The selected participants will be informed of the government approved laboratories near their
home which provide the required testing facilities and participants will be asked to pay the
costs of these additional tests up front. The cost of the test and transport to the
laboratory will be reimbursed to the participant after the participant sends the report of
this test to the Allergy and Asthma Institute, Pakistan (AAIP), physically or electronically,
and provides the original receipts of payment. Patients who have already had these tests done
will be excluded from the random selection, and their results collected and recorded.
