Clinical trial NCT04955327: To Compare the Efficacy and Tolerability of A. Paniculata/A. Chilensis in Individuals With URTI
Official title: A Double-blind, Randomized, Placebo-Controlled, Comparative Study for Assessing the Efficacy and Tolerability of A. Paniculata/A. Chilensis in Individuals With Upper Respiratory Tract Infections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Upper Respiratory Tract Infection
Lead sponsor: Vedic Lifesciences Pvt. Ltd.
Sponsor class: INDUSTRY
First posted: 2021-07-08
Enrollment: 225
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Conventional therapy of upper respiratory tract infection (URTI) is not always effective and sometimes leads to side effects and also to inappropriate use of antibiotic. Hence, a search for safe and effective further treatment options is justified and would be a welcome addition to available conventional treatment. Use of plant based dietary supplements has become increasingly popular over the last few decades or so. Research based on some plants is more than centuries old and its main therapeutic objective is to stimulate the self-healing power of the body. Andrographolide was docked successfully in the binding site of SARS-CoV-2 Mpro. Computational approaches also predicts this molecule to have good solubility, pharmacodynamics property and target accuracy. This molecule also obeys Lipinski's rule, which makes it a promising compound to pursue further biochemical and cell based assays to explore its potential for use against COVID-19. A. Paniculata is a patented extract, standardized to Andrographolide, 14-deoxyandrographolide, and Neo-andrographolide. Maqui contains Maqui Berry Extract of Aristotelia Chilensis (10% Anthocyanidin, 8% Delphinidin) belonging to the family of Elaeocarpaceae, which has been known for its use in several conditions such as sore throat, fever and several other ailments. In the present study, the therapeutic potential of Andrographis Paniculata and Aristotelia chilensis as single ingredients as well as in combination will be evaluated in participants with common cold and COVID related symptoms. The products to be evaluated have been rigorously standardized and are available under the brand names of A. Paniculata and A. Chilensis. Literature indicates that both A. Paniculata and A.Chilensis are effective and safe in the treatment of typical cold-related symptoms in adults.

Detailed description: The common cold is one of the most frequent minor illnesses in the world. A large US-American survey showed that over 70% of the population annually was suffering from at least one viral respiratory tract infection. Also the economic burden in the USA was almost USD 40 billion annually causing considerable direct and indirect healthcare costs. Caused by 200 identified types of viruses, the common cold is primarily associated with rhinoviruses. Common cold symptoms may include sore throat, runny nose, general malaise, and low-grade fever at onset, followed by nasal congestion and cough. While benign, they last for several days and cause 40% of all missed work days. Complications also include sinusitis, otitis media and pneumonia, exacerbations of asthma and chronic obstructive pulmonary disease, and serious illness in immunocompromised patients.

Colds typically afflict most adults and adolescents 2-4 times a year and symptoms usually peak around day 3 or 4 and last 1-2 weeks with a median of 7 days. There is no approved specific therapy for URTI, treatment is therefore mainly symptomatic. The most common pharmacological treatments are antipyretics, anti-inflammatory drugs, expectorants, decongestants, and cough suppressants, either alone or in combination. Supportive measures can include bed rest, hot baths, and inhalations, gargling, and drinking plenty of fluids. Antibiotics are widely prescribed, but often is inappropriate because URTI are mostly caused by viruses and are only indicated in the case of bacterial infection. Its overuse can also lead to the development of community acquired resistant pathogens which are an increasing and serious health burden.

Eligibility criteria: Inclusion Criteria:

1. Males and females aged between 18 and 50 years, complete as of the screening date.
2. Participants with symptoms of acute upper respiratory tract infection as assessed by the investigator at the time of screening.
3. Participants with BMI ≤ 29.9 kg/m2.
4. Upper respiratory tract infection symptoms present for at least 24 hours but not more than 72 hours prior to screening visit.
5. Those having a score of ≥ 5 for at least 2 symptoms out of runny nose, plugged nose, sneezing, sore throat, scratchy throat, cough or head congestion on the Wisconsin Upper Respiratory Symptom Survey-21.
6. Participants not requiring hospitalization.
7. Participants with COVID +ve/ COVID -ve RT-PCR report.
8. SPO2 level ≥ 90%
9. Systolic blood pressure \< 130 mm Hg and/or diastolic blood pressure \< 90.
10. Those who demonstrate an understanding of the study details and have a willingness to participate, as evidenced by voluntary written informed consent.
11. Must be literate and have the ability to complete the study-based questionnaires and requirements.

Exclusion Criteria:

1. High grade fever defined as body temperature ≥ 40°C.
2. With a history of allergy (allergic rhinitis) along with symptoms such as sneezing, runny nose and red, watery and itchy eyes.
3. Chest X-ray showing signs of pneumonia.
4. Participants with history of chronic obstructive pulmonary disease, pulmonary fibrosis or asthma
5. Participants with rhinitis medicamentosa, chronic cough of bacterial, fungal or other known origin.
6. Participants with anatomical nasal obstruction/ deformity or nasal reconstructive surgery etc.
7. Participants with history of heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies.
8. Participants with history of immunocompromised state immune system with/ without organ transplant.
9. Participants with known or suspected hypersensitivity or intolerance to herbal products.
10. Alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 2.0 times the upper limit of normal.
11. Participants diagnosed with Sickle cell disease, Thalassemia, Type I/ II diabetes mellitus, cystic fibrosis.
12. Diagnosed cases of hypertension.
13. Those not willing to abstain from home based cold remedies that include but are not limited to steam inhalation, decoctions, vapour rub, ginger tea, honey tea, decoctions, or any form of dietary supplements during the entirety of study participation period.
14. Those who have been vaccinated for influenza, swine flu or COVID three months prior to screening visit.
15. Those who have taken or should be taking or are taking antibiotics, antivirals, steroids, nasal decongestants, antihistamines or other medications that are expected to alleviate cold symptoms within one week of the start of the study.
16. Those who have severe mental illnesses, such as dementia, Parkinson's disease, Alzheimer's Disease, depression or anxiety disorders, or those who are currently taking psychoneurological drugs, such as antidepressants.
17. Those who have participated in other clinical trials within 30 days, prior to the screening visit or plan to participate in other clinical trials during the trial period.
18. Participants with substance abuse as per last two year history that includes the use of but is not limited to drugs such as cocaine, amphetamine, marijuana etc.
19. Individuals having a history of smoking or currently smoking or using any form of smokeless tobacco.
20. Participants with heavy alcohol consumption, defined as:

    1. For men: More than 14 standard alcoholic drink (SAD)/week or more than 4 SAD in a day.
    2. For women: More than 7 SAD/week or more than 3 SAD in a day.
    3. Binge drinkers, defined as 5 or more SAD for men, in a 2-hour time frame.
    4. Binge drinkers, defined as 4 or more SAD for Women, in a 2-hour time frame. (NOTE - A standard alcoholic drink contains approximately 14 grams of alcohol, which is equivalent to 12 ounces of beer (\~5% alcohol), 8.5 ounces of malt liquor (\~9% alcohol), 5 ounces of wine (\~12% alcohol), 3.5 ounces of fortified wine (e.g., sherry or port), or 1.5 ounces of liquor (distilled spirits; \~40% alcohol)
21. Those who have clinically significant disorder/s of cardiovascular, endocrine, lymphatic, respiratory, hepatobiliary, urinary, reproductive, central nervous system, musculoskeletal and digestive systems.
22. Females who are pregnant/planning to be pregnant/lactating or taking any oral contraceptives.
23. Any condition that could, in the opinion of the investigator, preclude the participant's ability to successfully and safely complete the study or that may confound study outcomes.

Primary outcomes:
measure: Severity Outcome
timeFrame: Day 0, 1, 2, 3, 4, 5, 6, and 7
Secondary outcomes:
measure: Time to resolve symptoms
timeFrame: Day 0, 1, 2, 3, 4, 5, 6, and 7
measure: percentage wise severity resolution
timeFrame: 7 days
measure: Minimal Important Difference
timeFrame: Day 0, 5, and 7
measure: Visual Analogue Scale based severity outcomes
timeFrame: Day 0, 1, 2, 3, 4, 5, 6, and 7
measure: Change in symptom resolution
timeFrame: Day 0 to day 7 (for all COVID +ve participants) and Day 8 to day 15 (For COVID participants who didn't turn negative on day 8)
Other outcomes:
Locations:
city: Mumbai
country: India
facility: St . George Hospital
state: Maharashtra
city: Nagpur
country: India
facility: Gillurkar Multispecialty Hospital
state: Maharashtra
city: Nagpur
country: India
facility: Shree Hospital & Critical Care Center
state: Maharashtra
city: Kanpur
country: India
facility: Apollo Spectra Hospitals
state: Uttar Pradesh
city: Varanasi
country: India
facility: Shubham Sudbhawana Super Specialty Hospital
state: Uttar Pradesh
Study officials:
References: