Effect of Kan-Jang® Supplementation in Patients Diagnosed With COVID-19: A Randomized, Quadruple-blind, Placebo-controlled Trial
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- Enrollment
- 140
- Locations
- 1
- Primary Endpoint
- Duration of infection
Study Overview
Brief Summary
The complexity of COVID-19 suggests a potential need for a range of therapies, including antiviral agents, immunostimulants, immunosuppressants, adaptogens, and anticoagulants. In this context, implementation of polyvalency drugs, which exhibit a wide range of biological activities and multitarget effects that is common for herbal medicines and specifically for Kan Jang, the fixed combination of Andrographis paniculata (Burm. F.) Wall. ex. Nees and Eleutherococcus senticosus (Rupr. & Maxim.) Maxim which are known to exhibit antiviral, immunomodulatory, and anti-inflammatory effects and clinical efficacy in the respiratory tract of patients with infectious diseases. The purpose of this study is to provide scientific evidence on the effectiveness of Kan Jang for the treatment of mild COVID-19. We hypothesize that Kan Jang will have superior efficacy in amelioration COVID symptoms compared to placebo with a comparable safety profile to placebo. We hypothesize that Kan Jang will increase patients' recovery rate and decrease the duration of illness.
The objective of the study is to assess the efficacy and tolerability of adjuvant treatment with Kan Jang for alleviating the severity of inflammatory symptoms (headache, loss of smell, gustatory dysfunction, rhinorrhea, nasal congestions, cough, sore throat, asthenia, myalgia, and fever) and shortening of their duration in mild COVID-19 patients.
Detailed Description
Rationale. Pathogenesis and progression of COVID-19 is a multistep process, which requires correct therapeutic strategy on various steps of initiation of overall defense response to pathogen and its resolution. Consequently, effective treatment of COVID-19 requires pharmaceutical corrections of many components innate, adaptive immune system, phases I-III metabolizing enzymes of detoxifying and repairing systems, and the SARS-Cov-2 virus' life cycle and proliferation.
It can be achieved by multitarget pharmaceutical intervention of herbal preparations with polyvalent and pleiotropic actions on host defense systems, e.g., adaptogens Andrographis paniculata L. (Burm. F.) Wall. ex. Nees and Eleutherococcus senticosus (Rupr. & Maxim.) Maxim, known as natural stress-protective plant extracts that increase adaptability, resilience, and survival of organisms.
A growing body of evidence suggests that extracts of Andrographis paniculata L. (SHA-10) and Eleutherococcus senticosus (SHE-3) are effective and well-tolerated medications for preventing and treating acute viral respiratory infections. WHO recognizes the use of Andrographis paniculata in the symptomatic treatment of upper respiratory infections, bronchitis, and pharyngotonsillitis. Recently, Thailand's health ministry approved using an Herba Andrographidis extract to treat the early stages of Covid-19 as a pilot program amid a flareup in the coronavirus outbreak in Thailand.
The fixed combination of these plants' extracts, the herbal medicinal product Kan Jang®, has been used in Scandinavia for treating symptoms of viral respiratory diseases, such as common colds and influenza, for >30 years. The clinical evidence accumulated indicates that Kan Jang has strong and, in many cases, significant effects on various common cold symptoms. In general, significant improvements were observed in nasal symptoms (e.g., secretion (g/day) frequency, and congestion, throat symptoms (soreness), respiratory problems (incl. cough, frequency of cough), headache, general malaise, fatigue, earache, sleep disturbance, and the objective parameter body temperature and decreased overall total symptoms scores in 5 days of treatment. Furthermore, Kan Jang® sped up patients' recovery and reduced post-influenza complications during the influenza viruses A1 and A3 periods in 1999 and 2000.
Both A. paniculata and E. senticosus and their fixed combination, Kan Jang®, exhibit antiviral, immunomodulatory, and anti-inflammatory effects. Kan Jang® is significantly more effective than the two active ingredients A. paniculata, and E. senticosus extracts alone, presumably due to synergistic interactions in molecular networks deregulated by Kan Jang. A recent study direct antiviral activity of Andrographis, Eleutherococcus, and their combination Kan Jang®, against coronavirus, has been demonstrated: Kan Jang significantly inhibits coronavirus growth in isolated human cells. The antiviral activity of the combinations of Andrographis and Eleutherococcus is more significant than expected. Further studies in COVID-19 patients are warranted to verify whether this observation of the direct antiviral activity of Kan Jang® has clinical significance.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
A Randomization Sequence of A and B from 1 to 140 will be generated by a qualified pharmacist (QP) at the manufacturing site before the study using a Random number generator. Treatment Randomization Sequence contains information about the distribution of unique random numbers between groups A and B. The QP will keep in secrecy for the clinic, and the investigators the Randomization Sequence and treatment code at the manufacturing site until the study is finalized. Study medications (boxes of placebo and Kan Jang capsules with identical appearance) will be labeled per Treatment Randomization Sequence. It will be provided to an independent statistician for statistical analysis of datasets when all patients complete the treatment. QP will disclose the treatment code providing the information about the actual assignment of treatments A and B to Kan Jang and placebo after statistical analysis of the results of a study where the data obtained from groups A and B will be compared.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Laboratory confirmed (SARS-Cov-2 PCR-positive test) mild COVID-19 infection (in the last three days),
- •COVID-19 patient in stable, moderate condition (i.e., not requiring Intensive Care Unit (ICU) admission).
- •Subjects must be under observation or admitted to a controlled facility or hospital (home quarantine is not sufficient).
- •Able to take medication alone
- •Able to give informed consent.
Exclusion Criteria
- •Pulmonary diseases
- •Chronic pulmonary diseases
- •Chronic rhinosinusitis
- •Patient admitted already under invasive mechanical ventilation;
- •The patient admitted with the severe acute respiratory syndrome and diagnosed with an etiologic agent other than Covid 19;
- •Renal failure requiring dialysis or creatinine ≥ 2.0mg/dl;
- •Tube feeding or parenteral nutrition.
- •Respiratory decompensation requiring mechanical ventilation.
- •Uncontrolled diabetes type
- •Hypertension stage 3,
- •Autoimmune disease.
- •Pregnant or lactating women.
- •Patients are taking antibiotics for a reason other than COVID-19 at enrollment.
- •Has a chronically weakened immune system (AIDS, lymphoma, chemo-radio- corticosteroid therapy, immunosuppressive pathology);
- •Patients treated with chemo-radio-corticosteroid therapy in the last six months.
- •Patients with active cancer.
- •Taking immunosuppressive drugs (e.g., anti-rejection treatment after organ transplant);
- •Already participating in another clinical trial;
- •Has any other condition that would prevent safe participation in the study.
Arms & Interventions
Kan Jang
70 patients take Kan Jang, two capsules three times a day for the two weeks in the treatment period. Daily dose - 90-120 mg of andrographolides.
Intervention: Kan Jang capsules (Drug)
Placebo
70 patients take Placebo, two capsules three times a day for the two weeks in the treatment period
Intervention: Placebo capsules (Other)
Outcomes
Primary Outcomes
Duration of infection
Time Frame: from Day 1 to Day 14 after randomisation
Time (days) from randomization to negative SARS-Cov-2 PCR test
Duration of symptoms of mild COVID-19: number of days before symptoms disappear
Time Frame: Change from baseline during the period of the treatment and follow up (from Day 1 to Day 14 and day 21 after randomization)
Time (days) from randomization to symptoms disappear
The severity of the COVID-19 total and individual symptoms: headache, loss of smell, gustatory dysfunction, rhinorrhoea, nasal congestions, cough, sore throat, asthenia, myalgia, and fever
Time Frame: Change from baseline during the period of the treatment and follow up (trough 21 days after randomization)
Time (days) from randomization to the relief of total and individual mild COVID symptoms scores.
Number of participants clinically recovered
Time Frame: Change from baseline during the period of the treatment and follow up (from Day 1 to Day 14 and day 21 after randomization)
Number of participants (n) without symptoms of mild COVID
Secondary Outcomes
- Severity of Respiratory symptoms and quality of life scores(Change from baseline during the period of the treatment and follow up (from Day 1 to Day 14 and day 21 after randomization))
- Cognitive performance test(Change from baseline during the period of the treatment and follow up (from Day 1 to Day 14 and day 21 after randomization))
- Immune response marker(Change from baseline during the period of the treatment and follow up (from Day 1 to Day 14 and day 21 after randomization))
- Hypercoagulation marker(Change from baseline during the period of the treatment and follow up (from Day 1 to Day 14 and day 21 after randomization)
- Inflammatory marker(Change from baseline during the period of the treatment and follow up (from Day 1 to Day 14 and day 21 after randomization))
- Physical activity(Change from baseline during the period of the treatment and follow up (from Day 1 to Day 14 and day 21 after randomization))