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

NCT ID: NCT05398965

Last Updated: 2022-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-18
• Study Completion Date: 2022-03-01

Brief 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. 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

Detailed Description

Detailed Objectives :

1. 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.

2. To document the effect of Eucalyptus oil on clinical symptoms improvement, including cough, anosmia, and sore throat.

3. To assess the effect of Eucalyptus oil on viral load indirectly reflected by the Real Time-Polymerase Chain Reaction/RT-PCR cycle threshold (CT)

4. To assess the effect of Eucalyptus oil on NLR, Interleukin-6, Interleukin-10, and Tumor Growth Factor-β (TGF-β) as inflammatory marker

5. 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 :

1. 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.

2. 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

1. Type 1 error 5%

2. Power of study 80%

3. superiority trial hypothesis

4. equal allocation for two arms

f. effect size is estimated at 0.7 total sample required : 52

Statistical Analysis

1. Intention to treat

2. Descriptive statistic

3. Repeated measurement analysis using mixed model analysis.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention Group

The group will receive standard COVID medication + Eucalyptus oil on external use for 14 days

Group Type: EXPERIMENTAL

Eucalyptus Oil

Intervention Type: DRUG

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 medication

Intervention Type: DRUG

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.

Comparator Group

The group will receive standard COVID medication only

Group Type: ACTIVE_COMPARATOR

Standard COVID medication

Intervention Type: DRUG

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.

Interventions

Eucalyptus Oil

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.

Intervention Type: DRUG

Standard 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.

Intervention Type: DRUG

Other Intervention Names

Herbal Roll On; COVID Medication

Eligibility Criteria

Inclusion Criteria

1. SARS-COV-2 infections were confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) from the nasopharyngeal swab.

2. 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%)

3. Sign the informed consent

4. Have not received the COVID-19 medicine yet

Exclusion Criteria

1. 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)

2. History of hepatitis or impaired liver function

3. 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)

4. Pregnant or lactating women

5. Allergy to any of the components of the test product

6. Participated in other clinical studies

Withdraw from the study:

The protocol treatment will be discontinued if the patient

1. Withdraw their consent based on the patient's demand

2. Patient's compliance of the use of test product <90% or >5 times not using the product according to the predetermined schedule

3. Severe adverse events occurred

4. After undergoing clinical trials, the patient experienced things that caused him/her to no longer meet the criteria set out in this protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Agriculture, Republic of Indonesia

UNKNOWN

Sponsor Role: collaborator

Hasanuddin University

OTHER

Sponsor Role: lead

Responsible Party

Bumi Herman

Assistant Lecturer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Arif Santoso, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Hasanuddin University

Idrus Paturusi, Prof.

Role: PRINCIPAL_INVESTIGATOR

Hasanuddin University

Nasrum Massi, Prof.

Role: PRINCIPAL_INVESTIGATOR

Hasanuddin University

Idrianti Idrus, MD

Role: PRINCIPAL_INVESTIGATOR

Hasanuddin University

Firdaus Hamid, MD. PhD

Role: PRINCIPAL_INVESTIGATOR

Hasanuddin University

Andi Rofian Sultan, MD. Ph.D

Role: PRINCIPAL_INVESTIGATOR

Hasanuddin University

Munawir Munawir, MD

Role: PRINCIPAL_INVESTIGATOR

Hasanuddin University

Rasiha Rasiha

Role: PRINCIPAL_INVESTIGATOR

Hasanuddin University

Locations

Hasanuddin University Hospital

Makassar, South Sulawesi, Indonesia

Countries

Indonesia

Other Identifiers

3105221321

Identifier Type: -

Identifier Source: org_study_id