GARGLES: Povidone-Iodine Vs Essential Oil Vs Tap Water Gargling For COVID-19 Patients

• Sponsor: Universiti Sains Islam Malaysia (Other)
• Overall Status: Completed
• CT.gov ID: NCT04410159
• Collaborator: Universiti Kebangsaan Malaysia Medical Centre (Other)
• Enrollment: 20
• Location: 1
• Arms: 4
• Actual Duration (Days): 14
• Patients Per Site Per Month: 43.5

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the ability of regular gargling to eliminate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the throat and nasopharynx. This 4 arms interventional study compares the effect of gargling using povidone-iodine, essential oils- based, tap water with control (no intervention) among Stage 1 coronavirus disease-2019 (COVID-19) patients.

Findings from this study will provide new insight into the importance of gargling in the treatment and prevention of COVID-19.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Povidone-Iodine; Drug: Essential oils; Other: Tap water	Phase 2

Detailed Description

Experimental plan

After consent is taken, all groups will be briefed regarding the study protocol separately.

• Group A will be briefed on the correct procedures of gargling with Betadine®. The participants will be instructed to take 10ml of povidone-iodine (PVP-I), tilt their heads backward and gargle for 30 seconds, three times per day for 7 days

• Group B will be briefed on the correct technique of gargling with Listerine®. The participants will be instructed to take 20ml of essential oils, tilt their heads backward and gargle for 30 seconds, three times per day for 7 days

• Group C will be briefed on the correct technique of gargling with hydrogen peroxide. The participants will be instructed to take 10ml of hydrogen peroxide, tilt their heads backward and gargle for 30 seconds, three times per day for 7 days

• Group D will be briefed about the involvement in this study. They will be managed according to the standard protocol of the hospital with no additional intervention.

Monitoring

1. Oropharyngeal and nasopharyngeal swabs will be taken on day 4, 6 of intervention, and day 12 post-intervention. The swabs will be subjected to detection of SARS-CoV-2 by real-time reverse transcriptase-polymerase chain reaction (rt RT-PCR).

2. Patients will be given a chart for them to record their gargling practice and symptoms (if any) during the intervention period ( 7 days)

3. Clinical data collection sheet will be provided to attending clinicians. The required information includes demographic data, daily vital signs, serial absolute lymphocytic count, LDH, chest radiograph, and symptoms. Clinical monitoring will be done until day 14 of the intervention.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 4 arms Gargle with povidone-iodine Gargle with essential oils Gargle with tap water Control4 arms Gargle with povidone-iodine Gargle with essential oils Gargle with tap water Control
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot, Open-Labelled, Randomised Controlled Trial Of Povidone-Iodine Vs Essential Oil And Tap Water Gargling For COVID-19 Patients
• Actual Study Start Date: Jun 22, 2020
• Actual Primary Completion Date: Jun 29, 2020
• Actual Study Completion Date: Jul 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Povidone-iodine gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days	Drug: Povidone-Iodine; Gargle; Other Names: Betadine
Experimental: Essential Oils gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days	Drug: Essential oils; Gargle; Other Names: Listerine
Experimental: Tap water gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days	Other: Tap water; Gargle
No Intervention: Control This group will receive the standard treatment protocol without any additional intervention

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Early Viral Clearance [Day 6]

   Viral clearance is defined as two negative RT-PCR (of swabs from oropharynx and nasopharynx) results at least 24 hours apart

Secondary Outcome Measures

1. Number of Participants With Negative RT-PCR Results [Day 12]

   RT-PCR (swabs from oropharynx and nasopharynx) taken at day 12

2. Number of Patients That Progress to More Severe Disease [Day 12]

   Presence of signs and symptoms of more severe COVID19 Based symptoms diary and clinical evaluation

3. Number of Patients With Abnormal Radiological Findings [Day 0-14]

   abnormal chest x-ray or CT scan

4. Number of Patients With Abnormal Laboratory Findings [Day 0-14]

   Abnormal absolute lymphocytic count Abnormal C-reactive protein

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. adult aged 18 years and above

2. able to understand instructions

3. Stage 1 COVID-19

4. < 5 days of illness or diagnosis

Exclusion Criteria:

1. Less than 18 years old

2. Unable to understand instructions

3. Stage 2 & 3 COVID-19

4. Respiratory symptoms or fever on admission

5. Abnormal chest radiograph or computed tomography (CT) findings on admission

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Universiti Kebangsaan Malaysia Medical Centre	Bandar Tun Razak	Wilayah Persekutuan Kuala Lumpur	Malaysia	56000

Sponsors and Collaborators

• Universiti Sains Islam Malaysia
• Universiti Kebangsaan Malaysia Medical Centre

Investigators

• Principal Investigator: NURUL A MOHAMED, Universiti Sains Islam Malaysia

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - May 1, 2020

More Information

Publications

• Dennison DK, Meredith GM, Shillitoe EJ, Caffesse RG. The antiviral spectrum of Listerine antiseptic. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995 Apr;79(4):442-8.
• Eggers M, Koburger-Janssen T, Eickmann M, Zorn J. In Vitro Bactericidal and Virucidal Efficacy of Povidone-Iodine Gargle/Mouthwash Against Respiratory and Oral Tract Pathogens. Infect Dis Ther. 2018 Jun;7(2):249-259. doi: 10.1007/s40121-018-0200-7. Epub 2018 Apr 9.
• Eggers M. Infectious Disease Management and Control with Povidone Iodine. Infect Dis Ther. 2019 Dec;8(4):581-593. doi: 10.1007/s40121-019-00260-x. Epub 2019 Aug 14. Review. Erratum in: Infect Dis Ther. 2019 Aug 22;:.
• Satomura K, Kitamura T, Kawamura T, Shimbo T, Watanabe M, Kamei M, Takano Y, Tamakoshi A; Great Cold Investigators-I. Prevention of upper respiratory tract infections by gargling: a randomized trial. Am J Prev Med. 2005 Nov;29(4):302-7.

• Responsible Party: NURUL AZMAWATI MOHAMED, Dr, Universiti Sains Islam Malaysia
• ClinicalTrials.gov Identifier: NCT04410159
• Other Study ID Numbers: USIMalaysia
• First Posted: Jun 1, 2020
• Last Update Posted: Jul 21, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by NURUL AZMAWATI MOHAMED, Dr, Universiti Sains Islam Malaysia: gargle; povidone-iodine; essential oils; tap water
• Additional relevant MeSH terms: COVID-19; Povidone-Iodine; Listerine; Povidone

Study Results

Participant Flow

Recruitment Details	All patients were recruited 2 to 3 days after date of diagnosis (nasophryngeal swab postive for SARS-C0V-2. All patients were asymptomatic and admitted to the hospital for observation
Pre-assignment Detail	No significant event occurred after enrollment

Arm/Group Title	Povidone-iodine	Essential Oils	Tap Water	Control
Arm/Group Description	gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle	gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle	gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle	This group will receive the standard treatment protocol without any additional intervention
Period Title: Overall Study
STARTED	5	5	5	5
COMPLETED	5	5	5	5
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Povidone-iodine	Essential Oils	Tap Water	Control	Total
Arm/Group Description	gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle	gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle	gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle	This group received the standard treatment protocol without any additional intervention	Total of all reporting groups
Overall Participants	5	5	5	5	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	5 100%	5 100%	5 100%	5 100%	20 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.4 (7.44)	34.4 (12.50)	30.8 (3.77)	24.8 (2.68)	30.6 (7.91)
Sex: Female, Male (Count of Participants)
Female	3 60%	1 20%	0 0%	0 0%	4 20%
Male	2 40%	4 80%	5 100%	5 100%	16 80%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	5 100%	5 100%	5 100%	5 100%	20 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Malaysia	5 100%	5 100%	5 100%	5 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Early Viral Clearance
Description	Viral clearance is defined as two negative RT-PCR (of swabs from oropharynx and nasopharynx) results at least 24 hours apart
Time Frame	Day 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Povidone-iodine	Essential Oils	Tap Water	Control
Arm/Group Description	gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle	gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle	gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle	This group will receive the standard treatment protocol without any additional intervention
Measure Participants	5	5	5	5
Count of Participants [Participants]	5 100%	4 80%	1 20%	0 0%

2. Secondary Outcome

Title	Number of Participants With Negative RT-PCR Results
Description	RT-PCR (swabs from oropharynx and nasopharynx) taken at day 12
Time Frame	Day 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Povidone-iodine	Essential Oils	Tap Water	Control
Arm/Group Description	gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle	gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle	gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle	This group will receive the standard treatment protocol without any additional intervention
Measure Participants	5	5	5	5
Count of Participants [Participants]	5 100%	4 80%	2 40%	1 20%

3. Secondary Outcome

Title	Number of Patients That Progress to More Severe Disease
Description	Presence of signs and symptoms of more severe COVID19 Based symptoms diary and clinical evaluation
Time Frame	Day 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Povidone-iodine	Essential Oils	Tap Water	Control
Arm/Group Description	gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle	gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle	gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle	This group will receive the standard treatment protocol without any additional intervention
Measure Participants	5	5	5	5
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

4. Secondary Outcome

Title	Number of Patients With Abnormal Radiological Findings
Description	abnormal chest x-ray or CT scan
Time Frame	Day 0-14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Povidone-iodine	Essential Oils	Tap Water	Control
Arm/Group Description	gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle	gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle	gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle	This group will receive the standard treatment protocol without any additional intervention
Measure Participants	5	5	5	5
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

5. Secondary Outcome

Title	Number of Patients With Abnormal Laboratory Findings
Description	Abnormal absolute lymphocytic count Abnormal C-reactive protein
Time Frame	Day 0-14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Povidone-iodine	Essential Oils	Tap Water	Control
Arm/Group Description	gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle	gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle	gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle	This group will receive the standard treatment protocol without any additional intervention
Measure Participants	5	5	5	5
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	Adverse event data were collected from day 1 of intervention until day 14
Adverse Event Reporting Description	Similar to clinicaltrial.gov
Arm/Group Title	Povidone-iodine		Essential Oils		Tap Water		Control
Arm/Group Description	gargle with povidone-iodine 10mL, 30 seconds, 3 times per day, 7 days Povidone-Iodine: Gargle		gargle with essential oils 20mL, 30 seconds, 3 times per day, 7 days Essential oils: Gargle		gargle with tap water 100 mL, 30 seconds, 3 times per day, 7 days Tap water: Gargle		This group will receive the standard treatment protocol without any additional intervention
All Cause Mortality
	Povidone-iodine		Essential Oils		Tap Water		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Serious Adverse Events
	Povidone-iodine		Essential Oils		Tap Water		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Povidone-iodine		Essential Oils		Tap Water		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)

Limitations/Caveats

Inadequate budget for laboratory test lead to small numbers of subjects analyzed

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.