RCT of gargles for Covid-19 patients

Farhan Raza Khan

BDS, MS, MCPS, FCPS

 I am trained in Operative Dentistry & Endodontics and possess excellent competency in Oral Implantology. I have been serving as a full time faculty at Aga Khan University Hospital, Karachi since 2007 where I am involved in poly-specialty Restorative Dentistry practice. I have been served as residency program director during 2009-2016. To date, I have supervised 15 residents as clinical residency (FCPS program) and mentored 10 graduate students in MSc Epidemiology and Biostatistics program.

On research front, I have published 71 PubMed indexed research articles in various. I am currently serving as a manuscript reviewer for 14 prestigious journals including Journal of Periodontology, Journal of Prosthodontics and BMC Oral Health. Currently I am engaged in getting grant for my following trial:

“A double blind, randomized controlled pilot trial of gargling agents in reducing intraoral viral load among laboratory confirmed COVID-19 patients: GARGLES STUDY”

If we are able to demonstrate effectiveness of topical anti-viral mouthwash and nasal lavage then not only dentists, other clinicians involved in aerosol generating procedures (ENT, maxillofacial and anesthesiologists) could be benefited by simply doing a pre-procedure mouthwash and nasal lavage as a prophylaxis before embarking upon an aerosol generating procedure. Moreover, such Gargles based prophylaxis can be part of the routine management of patients visiting outpatient clinics where the status of Covid-19 is not known.

The risk of morbidity and mortality is high among physicians and nurses involved in the screening and management of Covid-19 patients. Globally, over 230 physicians and surgeons have died while taking care of these patients. The cause of death was high exposure of viral load. The antiviral gargles and nasal lavage can decrease the fatalities among doctors and nurses.

This research is important as there is no definitive management for Covid-19 patients. At present, only preventive strategies such as frequent hand washing, use of mask, social distancing and avoidance of congregation is being followed. 

We have suggested a RCT to determine effectiveness of simple mouthwash and nasal lavage (with antiviral agents) as a prophylaxis against viral colonization. 

The present study will be the first to demonstrate that topical use of antiviral rinses could quantitatively reduce COVID-19 virus in the oro-naso-pharynx. Patients, physicians, nurses and dentists, all could be benefited with this findings of this study. Above all, if this is found to be effective, such gargles could be used as routine prophylaxis of patients visiting outpatient clinics where the status of COVID-19 is not known.

Our objective is to compare the effectiveness of Hydrogen peroxide, Povidone-Iodine and Hypertonic saline in reducing intra-oral viral load in COVID-19 positive patients. And to explore if Neem extract (Azardirachta indica) can be used as an antiviral gargle against COVID-19.

It will be a blinded-randomized controlled trial to be carried out on PCR confirmed Covid-19 patients. There will be five study groups. Group A (n=10) patients using 0.2% Povidone-Iodine gargles and nasal lavage for 20-30 seconds, thrice daily for 6 days. Group B (n=10) patients will be subjected to 1% Hydrogen peroxide, Group C (n=10) will use Neem extract solution and Group D (n=10) will use 2% hypertonic saline for a similar time period. Group E (n=10) will serve as positive controls using distilled water only. Study participants will continue to get their routine inpatient medical care. Baseline swab will be taken from the posterior pharyngeal wall on day 1 and the end-point swab on day 7. Primary outcome is the reduction in the intra-oral viral load confirmed with quantitative PCR. Repeated measures ANOVA and GEE will be used to compare the reduction in intra-oral viral load. This trial is registered at www.clinicaltrials.gov # NCT 04341688. 

If we are able to demonstrate effectiveness of topical anti-viral mouthwash and nasal lavage then not only dentists, other clinicians involved in aerosol generating procedures including ENT surgeons, maxillofacial surgeons and anesthesiologists) could be benefited by simply doing a pre-procedure mouthwash and nasal lavage as a prophylaxis before embarking upon an aerosol generating procedure. 

Moreover, such Gargles based prophylaxis can be part of the routine management of patients visiting any outpatient clinics where the status of Covid-19 is not known.

Pakistan is a resource restraint country, it’s not possible to carry out Covid-19 testing at mass scale. Simple, cost effective interventions against the pandemic is highly desirable. At present, only preventive strategies such as frequent hand washing, use of mask, social distancing and avoidance of congregation is being followed. We have suggested a RCT to determine effectiveness of simple mouthwash and nasal lavage (with antiviral agents) as a prophylaxis against viral colonization. If we are able to demonstrate the effectiveness of these topical agents then not only patients but physicians, nurses and dentists, all could be benefited with the study.

Being a dentist, I am routinely involved in aerosol generating procedures (such as tooth filling, root canal and crowns etc. With the current pandemic the dental procedures were abandoned all over the world fearing that aerosol generating procedures might increase the spread of Covid-19 virus.

the routine elective dentistry came to a halt. for emergency dental procedures, American dental association recommended use of  hydrogen peroxide but as a prudent dentist I could not find an evidence base for such a  recommendation. The Chinese dental associations on the other hand recommended use of Povidone-iodine as a pre-procedural mouth rinse. again its evidence in the literature is not well supported especially for Covid-19 virus.

Moreover, the local herbal medicines have started recommending Neem extracts (Azardirachta indica)as a potential topical antiviral agent. With this question in mind, I decided to plan a randomized controlled trial to determine the effectiveness of these agents compared against each other and hypertonic saline for laboratory confirmed Covid-19 patients.

I believe that we will able to explore the best mouthrinse and nasal lavage (by quantitative PCR) that could be used as a prophylaxis by physicians and nurses working in the covid wards to reduce viral loads in the oro-naso pharynx.

Moreover, this mouthwash/ nasal lavage solution could also help dentists and their patients limiting the spread of virus in the dental office.

I am a dentist well versed in clinical dentistry (over 20 years of clinical practice in University clinics setting) with strong research background (71 plus PubMed indexed publications) 

My co-investigators are dentists, ENT surgeons, Basic research scientists, virologist and immunologists having experience of research and publications in their respective fields.

Moreover, all of us are associated as full time faculty at a tertiary care university hospital (Aga Khan University hospital, Karachi, Pakistan) that is the biggest Covid-19 private sector facility in Pakistan. thus, we have knowledge, skills, experience and patients to do this study. all we need is funding to initiate the research.

Our study protocol is already approved by our department, hospital Clinical trial unit, chief Medical Officer's office and Associate Dean Research office. the protocol is already registered at the www.clinicaltrials.gov NCT 04341688.  

I started my career as a dentist but I did training in clinical research and epidemiology and biostatistics by sacrificing my clinical earnings just to mould my career as a clinician investigator. 

this has made me learn multi-tasking. In 2010, the residency program director in my department left and I was the only faculty meber eligible to salvage the program, so in addition to my clinical and research responsibilities, I undertook the position of residency directors and within 6 years I could train 12 FCPS clinical dentistry residents and 6 MSC epidemiology -Biostatistics graduate students as core supervisor. in thius way, I maintained a balance of clinical service, education & capacity building of post graduates along with research productivity in my department.

I served as program director for 6 years, section head for 2 years and chief of dental services (administrative position) for 2 years. However, I maintained research publications, clinical volumes and revenue generation and training of students are at an equilibrium that we sailed through hard times without compromising any of these important activities.