COVID-19Phase 2NCT05398965

Eucalyptus Oil as Adjuvant Therapy for Coronavirus Disease 19 (COVID-19)

A Phase 2 study testing Eucalyptus Oil and Standard COVID medication in people with COVID-19, run by Hasanuddin University at 1 site in Indonesia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Background : Based on several clinical trials, eucalyptus oil can suppress edema formation and reduce inflammation, where the effect of 1,8-cineole is due to the inhibition of cytokine secretion by T lymphocytes. Read more about this study

Who is it for?: Ages 18 to 59 years
Conditions the study is for: COVID-19
What is being tested?: Eucalyptus Oil and Standard COVID medication
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 54 participants
Where: 1 siteIndonesia
Study dates: 18 Nov 2020to 1 Mar 2022
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 59 years
All sexes
No healthy volunteers
Adult

Who may be able to join

SARS-COV-2 infections were confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) from the nasopharyngeal swab.
Mild to moderate clinical symptoms or with nasal cannula oxygen modality maximal oxygen 4 liters/minute (Moderate COVID-19 patients mean patients with clinical signs of pneumonia (fever, cough, shortness of breath, rapid breathing) but no signs of severe pneumonia including Oxygen Saturation ≥ 95%)
Sign the informed consent
Have not received the COVID-19 medicine yet

Who cannot join

They have or develop severe COVID-19 symptoms according to the COVID-19 diagnosis and treatment guidelines of Indonesian society of respiratory; respiratory distress (RR ≥30 breaths/min, oxygen saturation <95% at a rest state)
History of hepatitis or impaired liver function
Patients with or had a history of comorbid such as coronary heart disease, congestive heart disease, renal insufficiency, chronic liver disease, diabetes mellitus, uncontrolled hypertension or grade II hypertension or hypertensive crisis, immunocompromised, Central Nervous System disorders (such as stroke, epilepsy, Alzheimer's, and meningitis)
Pregnant or lactating women
Allergy to any of the components of the test product
Participated in other clinical studies

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Withdraw from the study:
The protocol treatment will be discontinued if the patient
Withdraw their consent based on the patient's demand
Patient's compliance of the use of test product <90% or >5 times not using the product according to the predetermined schedule
Severe adverse events occurred
After undergoing clinical trials, the patient experienced things that caused him/her to no longer meet the criteria set out in this protocol.

Trial locations and contacts

1 site in 1 country.

Indonesia1 site

Hasanuddin University Hospital
Makassar, South Sulawesi, 90245

Other trials in Indonesia

About this study

Official title: Eucalyptus Oil as Adjuvant Therapy for Coronavirus Disease 19 (COVID-19), a Randomized Open-label Clinical Trial

Background :

Based on several clinical trials, eucalyptus oil can suppress edema formation and reduce inflammation, where the effect of 1,8-cineole is due to the inhibition of cytokine secretion by T lymphocytes. This but not limited to the reduction of interleukin (IL) of IL-4, IL-5, and IL-10 in nasal lavage fluids and levels of IL- 1β, IL-6, Tumor Necrosis Factor-α (TNF-α), and Interferon-γ (IFN-γ) in lung tissue of mice infected with influenza virus. Hence the researchers assume that Eucalyptus may possess benefits in COVID-19 as adjuvant therapy.

Objectives :

The primary objective of this study is to evaluate the efficacy of Eucalyptus oil as adjuvant therapy in mild-moderate COVID-19 patients.

Hypothesis :

Eucalyptus oil may reduce the inflammatory cytokines which eventually improves clinical symptoms

Read the detailed description

Detailed Objectives :

To assess the safety of Eucalyptus oil as an adjuvant to the standard of care in treating patients with mild to moderate COVID-19 symptoms.
To document the effect of Eucalyptus oil on clinical symptoms improvement, including cough, anosmia, and sore throat.
To assess the effect of Eucalyptus oil on viral load indirectly reflected by the Real Time-Polymerase Chain Reaction/RT-PCR cycle threshold (CT)
To assess the effect of Eucalyptus oil on NLR, Interleukin-6, Interleukin-10, and Tumor Growth Factor-β (TGF-β) as inflammatory marker
To assess the effect of Eucalyptus oil on immunoglobulin (Ig) M and G in patient's serum

Target population:

Patients with mild-moderate COVID-19

Setting:

Hospital and outpatient care

Intervention:

External use of Eucalyptus oil

Subject Recruitment and Screening :

A written, signed, and dated (ICF) consent form will be obtained from the patient before the study's inclusion. Assessment and records of patient's clinical report forms including demographic data, comorbidities and concurrent medications, symptoms experienced by the patient, body weight, height of the body, body mass index, vital signs, and fingertip oxygen saturation.
Baseline laboratory tests including complete blood count (CBC), neutrophil-lymphocyte ratio (NLR), liver (alanine aminotransferase (ALT), aspartate aminotransferase (AST), kidney function tests (serum creatinine), serum ferritin, blood glucose, coagulation test (prothrombin time and activated partial thromboplastin time), cytokine level (IL-6, IL-10, and TGF-β) will be assessed. On admission, computed tomography (CT) scan of the chest will also be performed.

Detailed procedures :

Eucalyptus oil will be applied to the surgery mask, 4 times a day, which is 45 minutes duration in each session for 14 days. Clinical assessment and vital signs, and follow-up RT-PCR tests by nasopharyngeal swab will be documented on days 5, 10, and 15. Follow-up laboratory results for blood, liver function, kidney function, blood glucose, cytokine level, and CT scan will be performed on Day 15. If moderate COVID-19 patients confirmed negative RT-PCR test results in 2 consecutive tests, the patient is allowed to be discharged and continue their adjuvant treatment at home (in the intervention group).

Sample size estimation :

following the sample size estimation of two different means

Type 1 error 5%
Power of study 80%
superiority trial hypothesis
equal allocation for two arms
effect size is estimated at 0.7 total sample required : 52

Statistical Analysis

Intention to treat
Descriptive statistic
Repeated measurement analysis using mixed model analysis.

Conditions: COVID-19
Being tested: Eucalyptus Oil, Standard COVID medication
Keywords: COVID-19, Eucalyptus, Viral Clearance, Cytokine Level, Clinical Improvement
Medical subject headings: COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Eucalyptus OilDrug
Also called Herbal Roll On
The Eucalyptus Oil pack contains Oleum Eucalyptus citriodora, Oleum Eucalyptus globulus, and Peppermint oil, given 4 times daily for 45 minutes each frequency, applied to the mask.
Standard COVID medicationDrug
Also called COVID Medication
This standard treatment is personalized according to the severity but is not limited to standard antiviral therapy, azithromycin 500 mg a day, vitamin C 500 mg 8 hourly a day, zinc 20 mg a day, tablet of complex vitamin B, and other symptomatic treatments.

Study groups in NCT05398965
Study group	Role	What they receive
Intervention Group	Experimental	The group will receive standard COVID medication + Eucalyptus oil on external use for 14 days Receives: Drug: Eucalyptus Oil; Drug: Standard COVID medication
Comparator Group	Active comparator	The group will receive standard COVID medication only Receives: Drug: Standard COVID medication

What is being measured

The primary outcome is the main question the study is designed to answer.

Clinical Symptoms
The patient will be asked for clinical improvement (three symptoms, sore throat, anosmia and cough) with a 6-likert scale question for each symptoms. Higher number (5) indicates very severe symptoms whereas 0 indicates no symptoms.
Measured: change of score for each symptoms from baseline to day 15
Viral clearance
level of Severe Acute Respiratory Corona Virus 2 (SARS-COV2) on nasopharyngeal sample measured by RT-PCR in Cycle Threshold Unit (CT)
Measured: change of CT Value from baseline to day 15
Neutrophil-Lymphocyte Ratio (NLR)
This ratio is used as a marker of subclinical inflammation. It is calculated by dividing the number of neutrophils by number of lymphocytes from the blood sample
Measured: change of NLR from baseline to day 15

Secondary outcomes (2)

Radiology improvement
the Radiology improvement of lung Computed Tomography (CT-Scan) on day 15 indicates by resolution or absence of inflammatory sign or abnormal findings (binary response)
Measured: change of radiology feature from baseline to day 15
Cytokine level
reduction of pro-inflammatory cytokine level in blood samples (Interleukin-6, Interleukin-10, Tumor Growth Factor/TGF-β)
Measured: change of cytokine level from baseline to day 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Nov 20201 Mar 2022

First posted1 Jun 2022
Study start18 Nov 2020
Primary completion28 Jan 2021
Study completion1 Mar 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for COVID-19Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Patients will be randomized into 2 study groups before starting their medication. The first group was only given standard COVID-19 therapy. While the treated group will be given standard COVID-19 along with adjuvant therapy (Eucalyptus oil on external use)
Masking: None (open label)
Enrolment: 54 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05398965
Sponsor's protocol ID: 3105221321
Status last verified: May 2022
First submitted: 31 May 2022
Last updated: 1 Jun 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 1 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Eucalyptus Oil as Adjuvant Therapy for Coronavirus Disease 19 (COVID-19), a Randomized Open-label Clinical Trial
ClinicalTrials.gov ID: NCT05398965
Acronym / sponsor ID: 3105221321
Conditions: COVID-19
Keywords: COVID-19, Eucalyptus, Viral Clearance, Cytokine Level, Clinical Improvement
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 54 participants (actual)
Lead sponsor: Hasanuddin UniversityUniversity, hospital or other
Collaborators: Ministry of Agriculture, Republic of Indonesia
Study start: 18 Nov 2020 (actual)
Primary completion: 28 Jan 2021 (actual)
Study completion: 1 Mar 2022 (actual)
First posted: 1 Jun 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Background :

Objectives :

The primary objective of this study is to evaluate the efficacy of Eucalyptus oil as adjuvant therapy in mild-moderate COVID-19 patients.

Hypothesis :

Eucalyptus oil may reduce the inflammatory cytokines which eventually improves clinical symptoms

Detailed description

Detailed Objectives :

To assess the safety of Eucalyptus oil as an adjuvant to the standard of care in treating patients with mild to moderate COVID-19 symptoms.
To document the effect of Eucalyptus oil on clinical symptoms improvement, including cough, anosmia, and sore throat.
To assess the effect of Eucalyptus oil on viral load indirectly reflected by the Real Time-Polymerase Chain Reaction/RT-PCR cycle threshold (CT)
To assess the effect of Eucalyptus oil on NLR, Interleukin-6, Interleukin-10, and Tumor Growth Factor-β (TGF-β) as inflammatory marker
To assess the effect of Eucalyptus oil on immunoglobulin (Ig) M and G in patient's serum

Target population:

Patients with mild-moderate COVID-19

Setting:

Hospital and outpatient care

Intervention:

External use of Eucalyptus oil

Subject Recruitment and Screening :

A written, signed, and dated (ICF) consent form will be obtained from the patient before the study's inclusion. Assessment and records of patient's clinical report forms including demographic data, comorbidities and concurrent medications, symptoms experienced by the patient, body weight, height of the body, body mass index, vital signs, and fingertip oxygen saturation.
Baseline laboratory tests including complete blood count (CBC), neutrophil-lymphocyte ratio (NLR), liver (alanine aminotransferase (ALT), aspartate aminotransferase (AST), kidney function tests (serum creatinine), serum ferritin, blood glucose, coagulation test (prothrombin time and activated partial thromboplastin time), cytokine level (IL-6, IL-10, and TGF-β) will be assessed. On admission, computed tomography (CT) scan of the chest will also be performed.

Detailed procedures :

Sample size estimation :

following the sample size estimation of two different means

Type 1 error 5%
Power of study 80%
superiority trial hypothesis
equal allocation for two arms
effect size is estimated at 0.7 total sample required : 52

Statistical Analysis

Intention to treat
Descriptive statistic
Repeated measurement analysis using mixed model analysis.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: Patients will be randomized into 2 study groups before starting their medication. The first group was only given standard COVID-19 therapy. While the treated group will be given standard COVID-19 along with adjuvant therapy (Eucalyptus oil on external use)

Arm	Type	Receives
Intervention Group	Experimental	Drug: Eucalyptus Oil, Drug: Standard COVID medicationThe group will receive standard COVID medication + Eucalyptus oil on external use for 14 days
Comparator Group	Active comparator	Drug: Standard COVID medicationThe group will receive standard COVID medication only

Who may qualify

Ages: 18 to 59 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (4 listed)

SARS-COV-2 infections were confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) from the nasopharyngeal swab.
Mild to moderate clinical symptoms or with nasal cannula oxygen modality maximal oxygen 4 liters/minute (Moderate COVID-19 patients mean patients with clinical signs of pneumonia (fever, cough, shortness of breath, rapid breathing) but no signs of severe pneumonia including Oxygen Saturation ≥ 95%)
Sign the informed consent
Have not received the COVID-19 medicine yet

Key exclusion criteria (12 listed)

They have or develop severe COVID-19 symptoms according to the COVID-19 diagnosis and treatment guidelines of Indonesian society of respiratory; respiratory distress (RR ≥30 breaths/min, oxygen saturation <95% at a rest state)
History of hepatitis or impaired liver function
Patients with or had a history of comorbid such as coronary heart disease, congestive heart disease, renal insufficiency, chronic liver disease, diabetes mellitus, uncontrolled hypertension or grade II hypertension or hypertensive crisis, immunocompromised, Central Nervous System disorders (such as stroke, epilepsy, Alzheimer's, and meningitis)
Pregnant or lactating women
Allergy to any of the components of the test product

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Eucalyptus OilAlso: Herbal Roll OnThe Eucalyptus Oil pack contains Oleum Eucalyptus citriodora, Oleum Eucalyptus globulus, and Peppermint oil, given 4 times daily for 45 minutes each frequency, applied to the mask.	Drug	Intervention Group
Standard COVID medicationAlso: COVID MedicationThis standard treatment is personalized according to the severity but is not limited to standard antiviral therapy, azithromycin 500 mg a day, vitamin C 500 mg 8 hourly a day, zinc 20 mg a day, tablet of complex vitamin B, and other symptomatic treatments.	Drug	Comparator Group, Intervention Group

Primary outcome

Clinical Symptoms
Time frame: change of score for each symptoms from baseline to day 15
The patient will be asked for clinical improvement (three symptoms, sore throat, anosmia and cough) with a 6-likert scale question for each symptoms. Higher number (5) indicates very severe symptoms whereas 0 indicates no symptoms.
Viral clearance
Time frame: change of CT Value from baseline to day 15
level of Severe Acute Respiratory Corona Virus 2 (SARS-COV2) on nasopharyngeal sample measured by RT-PCR in Cycle Threshold Unit (CT)
Neutrophil-Lymphocyte Ratio (NLR)
Time frame: change of NLR from baseline to day 15
This ratio is used as a marker of subclinical inflammation. It is calculated by dividing the number of neutrophils by number of lymphocytes from the blood sample

2 secondary outcomes

Radiology improvement
Time frame: change of radiology feature from baseline to day 15
Cytokine level
Time frame: change of cytokine level from baseline to day 15

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2022.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Arif Santoso, MD, Ph.D principal investigator

Hasanuddin University

Idrus Paturusi, Prof. principal investigator

Hasanuddin University

Nasrum Massi, Prof. principal investigator

Hasanuddin University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Eucalyptus Oil and Standard COVID medication in people with COVID-19, run by Hasanuddin University at 1 site in Indonesia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Symptoms (time frame: change of score for each symptoms from baseline to day 15). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05398965.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2022.