Clinical trial NCT05398965: Eucalyptus Oil as Adjuvant Therapy for Coronavirus Disease 19 (COVID-19)
Official title: Eucalyptus Oil as Adjuvant Therapy for Coronavirus Disease 19 (COVID-19), a Randomized Open-label Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Keywords: COVID-19
Eucalyptus
Viral Clearance
Cytokine Level
Clinical Improvement
Lead sponsor: Hasanuddin University
Sponsor class: OTHER
Collaborators: name: Ministry of Agriculture, Republic of Indonesia
First posted: 2022-06-01
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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)
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Clinical Symptoms
timeFrame: change of score for each symptoms from baseline to day 15
measure: Viral clearance
timeFrame: change of CT Value from baseline to day 15
measure: Neutrophil-Lymphocyte Ratio (NLR)
timeFrame: change of NLR from baseline to day 15
Secondary outcomes:
measure: Radiology improvement
timeFrame: change of radiology feature from baseline to day 15
measure: Cytokine level
timeFrame: change of cytokine level from baseline to day 15
Other outcomes:
Locations:
city: Makassar
country: Indonesia
facility: Hasanuddin University Hospital
state: South Sulawesi
Study officials:
affiliation: Hasanuddin University
name: Arif Santoso, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasanuddin University
name: Idrus Paturusi, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasanuddin University
name: Nasrum Massi, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasanuddin University
name: Idrianti Idrus, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasanuddin University
name: Firdaus Hamid, MD. PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasanuddin University
name: Andi Rofian Sultan, MD. Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasanuddin University
name: Munawir Munawir, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasanuddin University
name: Rasiha Rasiha
role: PRINCIPAL_INVESTIGATOR
References: