Coadministration of AYUSH 64 as an adjunct to Standard of Care in mild and moderate COVID-19: A randomised, controlled, multicentric clinical trial

TL;DR: In this article, the authors compared the co-administration of an Ayurvedic drug AYUSH 64 as an adjunct to standard of care (SOC) and SOC for efficacy and safety in the management of COVID-19.

Abstract: ObjectivesTo compare the co-administration of an Ayurvedic drug AYUSH 64 as an adjunct to standard of care (SOC) and SOC for efficacy and safety in the management of COVID-19. DesignMulticentre, parallel efficacy, randomized, controlled, open label, assessor blind, exploratory trial with a convenience sample. Patients followed to complete 12 weeks of study duration. SettingCOVID-19 dedicated non-intensive care wards at 1 government hospital, 1 medical college teaching hospital and 1 medical university teaching hospital Participants140 consenting, eligible, hospitalized adult patients suffering from mild and moderate symptomatic COVID-19 and confirmed by a diagnostic (SARS-CoV-2) RT-PCR assay on nasal and throat swab were randomized to SOC or SOC plus AYUSH 64. To be withdrawn if disease becomes severe. InterventionsTwo tablets of AYUSH 64, 500 mg each, twice daily after meals, and continued till study completion. SOC (symptomatic and supportive) as per national guidelines of India for mild and moderate disease. Main outcome measuresTime period to clinical recovery (CR) from randomization baseline and proportion with CR within 28 days time frame; CR defined in the protocol Results140 patients randomized (70 in each arm); 138 patients with CR qualified for analysis. Both groups were matched at baseline. The mean time to CR from randomization was significantly superior in AYUSH 64 group (95% CI -3.03 to 0.59 days); a higher proportion (69.7%) in the first week (p=0.046, Chi-square). No significant differences observed for COVID-19 related blood assays (such as D-Dimer). AYUSH 64 arm showed significant (p<0.05) superior persistent improvement in general health, quality of life, fatigue, anxiety, stress, sleep and other psychosocial metrics. 1 patient on SOC required critical care. 48 adverse events (AE) reported in each group. Barring three SAE (in SOC), AE were mild and none were drug related. 22 participants (8 on AYUSH) were withdrawn. No deaths were reported. ConclusionsAYUSH 64 hastened recovery, reduced hospitalization and improved overall health in mild and moderate COVID-19 when co-administered with SOC under medical supervision. It was safe and well tolerated. Further studies are warranted. Trial registrationThe Clinical Trials Registry India Number CTRI/2020/06/025557 FundingCCRAS, Ministry of AYUSH, Government of India

Summary

INTRODUCTION

• The world continues to reel under the tragic burden of the COVID-19 pandemic.
• Several drug trials were completed and many more are underway to unravel the evidence-based medicine (EBM) for more effective and safe management (1).
• The treatment of mild- moderate COVID-19 remains empirical, symptomatic and supportive (2, 3).
• The search to repurpose drugs (COVID-19) also rekindled vigorous research in the traditional, complementary and alternative systems of medicine (TCAM) (8,9).
• Based on Ayurvedic logic and clinical experience, AYUSH-64 was considered for repurpose therapeutic use in COVID-19.

METHODS

• This was a prospective, randomized, open label (assessor blind), two arm multicentre study with an exploratory research design and was planned and carried out during the COVID-19 pandemic (May-Nov 2020).
• The study was carried out in accordance with the principles of Good Clinical Practice (GCP), Declaration of Helsinki (Brazil update 2013), ICMR (Indian Council of Medical Research) and MoA/CCRAS Guidelines (2018) (23, 24).
• The protocol and the study report also complied with CONSORT guidelines (25).
• The study was monitored by an independent data safety monitoring board and a monitoring committee appointed by the sponsor.
• The overall scheme of the study, study procedures and predetermined time points of evaluation are shown in Fig 1.

Patients

• Voluntary hospitalized patients suffering from mild and moderate symptomatic COVID-19 were selected and after signing informed consent were screened for eligibility.
• Patients were jointly examined throughout the study by a modern medicine and Ayurveda physician (study investigator).
• All patients were managed for COVID-19 by an attending physician designated by the hospital at study site and who remained blinded to the treatment allocation in the trial (assessor blind).
• Adult patients with a typical clinical phenotype of COVID-19 illness and a laboratory confirmation test for SARS-CoV-2 (RT-PCR on a nasal and/or throat swab) were selected.
• Full details of the inclusion and exclusion criteria can be accessed in the protocol registered at CTRI website (26).

Trial Procedures

• Patients at each site were randomized to a SOC arm or AYUSH 64 (investigational product) along with SOC (AYUSH plus) in 1:1 ratio on a first come first serve basis.
• A central randomization schedule was prepared by a biostatistician (SS) using a standard statistical software and in blocks of 20 participant each.
• The randomized blocks were provided online with restricted access only to the principal investigator at each site as per the allotted sample size.

Standard of care

• All patients were begun on SOC soon after hospital admission as per the clinical judgement of the attending hospital physician.
• The concomitant use of hydroxychloroquine, azithromycin, corticosteroids, antibiotics, ivermectin, zinc, vitamin C, antiplatelet agents was as per the national guidelines of India but there were some local instructions as well (3).
• All patients were closely monitored on a daily basis as per standard COVID-19 protocol and which included respiration and peripheral arterial oxygen saturation, body temperature and blood pressure (3).

Investigational drug

• Each 500 mg tablet of AYUSH 64 contained aqueous extracts (100 mg each) of Alstonia scholaris (bark), Picrorhiza kurroa , Swertia chirata (whole plant) and Caesalpinia crista (200 mg seed powder).
• AYUSH 64 was procured from Indian Medicines Pharmaceutical Corporation Limited , Uttarakhand, India under arrangements with CCRAS, New Delhi.
• Each question was answered on a 100 mm horizontal visual analogue scale (VAS) which was anchored at either end (0 and 100 mm) for the worst or best outcomes.
• A comprehensive description of WHO QOL BREF (Text Box S2.1) and HR-BHF questionnaire including pre-study validation (Text Box S2.2, Text box S 2.3) is provided in the Supplementary File S2.
• Data was collected on a daily basis till discharge from the hospital following clinical recovery.

Outcome measures

• The primary efficacy measure was (i) the mean duration (days) from baseline randomization to day one of clinical recovery (CR) (ii) Proportion of patients showing clinical recovery within a time framework of 28 days.
• There were several secondary efficacy measures pertaining to (i) time lines such as mean duration from onset of symptoms to CR, mean duration from hospitalization to CR (ii) COVID19 related blood assay biomarkers such as C-reactive protein (CRP), D-Dimer, Ferritin, interleukin-6.

Study Withdrawals

• Patients worsening clinically and requiring prolonged oxygen and/or intensive care was withdrawn from the study and continued routine management in the hospital.
• All patients who were withdrawn were thoroughly questioned and evaluated to determine the reason for withdrawal.
• Patients were permitted to withdraw without assigning any reason.

Statistical Analysis

• A convenience study sample of 140 participants was finalized by AC and SS and considered adequate to address the study research questions.
• The data were analysed for central tendencies (mean, median), range, standard error, standard deviation and 95% confidence interval (95% CI).
• Statistical tests were carried out to compare treatment groups as per the distribution Student’s T test , Mann-Whitney statistic (non-parametric), Chi-square statistic , ANOVA.
• Both intent-to-treat and per protocol completer analysis were performed when appropriate.
• The study arm of ‘AYUSH 64 plus SOC’ is referred to as ‘AYUSH plus’ and ‘SOC alone’ is referred to as ‘SOC’ in the current paper.

RESULTS

• Total 140 patients were randomized with 70 patients in each of the two study arms.
• Fig 2 shows the patient disposition and withdrawals.
• One patient in the SOC worsened and was withdrawn; recovered after intensive medical care.
• 138 patients completed treatment as per protocol.
• None of the patients withdrawn reported a drug related AE.

Randomization Baseline

• Both the study groups were well matched for several demographic, clinical and laboratory variables as shown in Table 1.
• Most participants were men in the age range 30 -55 years.
• COVID-19 was classified mild in 80% participants.
• The study arms were well matched for several timelines at randomization baseline such as’ onset of symptom to hospital admission’ (-1.34 to 1.72),’ hospital admission to randomization’ (-0.17 to 0.39) and ‘symptom onset to randomization’ (-1.08 to 1.98); 95% CI of the difference between the group means (days) shown in parenthesis (Table 1).
• Skiagram of chest was reported (by radiologist) normal in 47% patients, mild abnormalities in 51% patients and moderate abnormalities in 2% patients in the AYUSH plus; correspondingly 46%, 41% and 13% in the SOC.

Efficacy

• Four participants started AYUSH 64 after 36 hours of randomization and were excluded from the primary efficacy analysis; addition of their data did not materially change the outcome (data not shown).
• The latter improvement was observed at each of the study site.
• None of the patients with radiological abnormalities complained of fever, persistent cough or breathlessness during the post hospital discharge follow up.
• There were no clinical diagnosed post-COVID lung complications diagnosed on study completion; skiagrams for several patients were reported normal.
• In comparison to SOC, AYUSH 64 plus showed significant improvement in several domains (physical health, psychological health, social relationship and environmental well-being) in the WHO QOL BREF and the total HR-BHF score on clinical recovery and during pre-determined follow up evaluations (Table 4).

Safety and related issues

• Additional data on AE as per predetermined study time points in each of the treatment arms is shown in Supplementary File S4, Table S4.1.
• No AE recorded for disorders of blood and lymphatic, immune system, metabolism and nutrition, psychiatric, reproductive system and breast, eye, vascular system, congenital familial and genetic, injury poisoning and procedural complications, and surgical and medical procedures;.
• None of the AE were considered causally related to AYUSH 64 or any other drug used in the study.
• One patient in the SOC group developed mild peripheral polyneuritis following recovery which was later diagnosed Guillain Barre syndrome (GBS); patient recovered completely.
• Repeated routine laboratory assays remained within normal limits in the two arms and there were no significant differences in the treatment arms (Supplementary File S5, Table S5.1).

DISCUSSION

• This study compared a combination regimen of AYUSH 64 and SOC (AYUSH plus) with SOC to treat patients suffering from mild and moderate COVID-19 and admitted in the hospital.139 of the 140 randomized patients achieved complete recovery.
• The current AYUSH 64 drug trial needs to be viewed against this perspective.
• It needs to be medically supervised and patients suitably counselled as was done in the current study.
• Mild and moderate cases may develop post COVID-19 complications (34).
• A similar reduction in the length of hospital stay was reported in a meta-analysis of controlled drug trials of coadministration of Chinese herbal medicine with conventional western medicine in COVID-19 (95 % CI of the mean difference was -3.28 to -0.70 days) (8).

Strengths and Limitations

• The current study repurposed a standardized Ayurvedic polyherbal formulation in popular Ayurveda practise for over three decades to improve the efficacy of SOC treatment in COVID-19.
• Importantly, patients showed persistent improvement in physical and mental health and quality of life.
• None of the patients in AYUSH plus arm worsened and there were no deaths in the study cohort.
• The authors believe that the current study has boldly addressed the need for evidence-based medicine to treat mild and moderate COVID-19.
• Several limitations were imposed by the chaotic and tragic pandemic situation.

Other Studies

• Several drug trials using Ayurveda and other CAM therapies in COVID-19 were registered in the clinical trial registry of India but a few are published (36, 46).
• The latter studies required MAB intervention within 24-48 hours of the illness onset and a firm diagnosis.
• This and several other restrictions described in the drug trial studies are likely to complicate widespread acceptance and clinical use, and more so in settings such as ours with several limitation in socioeconomics and medical care (49,50).
• The recent data on the use of repurposed and adjuvant drugs in hospital patients with COVID-19 did not make any mention of herbal drugs or other CAM therapies (51).
• It is likely that the use of Ayurveda and other CAM therapies such as AYUSH 64, both in the hospital and community setting, was several folds more and the authors need more suitable data (18).

Future Research

• AYUSH 64 needs to be evaluated in a suitable designed phase III drug trial.
• The latter study should also evaluate the likely role of AYUSH 64 to block progression to severe disease and reduce post COVID-19 complications.
• Experimental evidence is required to validate its anti-viral and salubrious effect on health and QOL.

CONCLUSION

• In a randomized controlled prospective study of hospitalized patients suffering from mild and moderate COVID-19, AYUSH 64 (a standardized polyherbal Ayurveda drug) was shown to be a significantly effective and safe adjunct to SOC.
• It hastened clinical recovery, reduced hospitalization period and showed early persistent substantial benefit towards physical and mental health.

Figures

Table 1: Baseline data on demographic, clinical, selected laboratory variables and SOC drugs: A randomized controlled study to evaluate the co-administration of AYUSH 64 with Standard of Care in COVID-19

Table 5: Number of participants with adverse events (AE), causality and worsening in a randomized controlled study to evaluate the co-administration of AYUSH-64 with Standard of Care (SOC) in mild and moderate symptomatic COVID-19 (n=139)

Table 4: Quality of life questionnaires scores (Secondary outcome): a randomized controlled study to evaluate the co-administration of AYUSH-64 with Standard of Care (SOC) in mild and moderate symptomatic COVID-19 (n=139)

Table 3: COVID-19 biomarkers: a randomized controlled study to evaluate the coadministration of AYUSH-64 with Standard of Care (SOC) in mild - moderate symptomatic COVID-19 (n=139); [Mean (days)± Standard Deviation]

Table 2: Primary efficacy measure (randomization to clinical recovery) and selected timeline: A randomized controlled study to evaluate the co-administration of AYUSH-64 with Standard of Care (SOC) in mild - moderate symptomatic COVID-19 (n=139);[Mean (days)± Standard Deviation]

Figure 2: Patient disposition and withdrawals: a randomized controlled study to evaluate the coadministration of AYUSH-64 with Standard of Care (SOC) in mild - moderate symptomatic COVID-19 of 12 weeks duration (n=140)

Figure 1: Study Flow diagram showing Study Events and Timelines: A randomized controlled study to evaluate the co-administration of AYUSH 64 with Standard of Care in COVID-19

Full text

1
Coadministration of AYUSH 64 as an adjunct to Standard of Care in mild
and moderate COVID-19: A randomised, controlled, multicentric clinical trial
Arvind Chopra
1
, Girish Tillu
2
, Kuldeep Chuadhary
3
,
Govind Reddy
4
, Alok Srivastava
5
, Muffazal
Lakdawala
6
, Dilip Gode
7
, Himanshu Reddy
8
, Sanjay Tamboli
9
, Manjit Saluja
1
, Sanjeev
Sarmukkaddam
1
, Manohar Gundeti
3
, Ashwinikumar Raut
10
, BCS Rao
11
, Babita Yadav
11
,
Narayanam Srikanth
11
, Bhushan Patwardhan
2
Authors’ affiliation
1. Centre for Rheumatic Diseases, Pune, India
2. Interdisciplinary School of Health Sciences, Savitribai Phule Pune University, Pune, India
3. Central Ayurveda Research Institute, Mumbai, India
4. Regional Ayurveda Research Institute, Nagpur, India
5. Regional Ayurveda Research Institute, Lucknow, India
6. H.N. Reliance Foundation Hospital and Research Centre, Mumbai, India
7. Datta Meghe Institute of Medical Sciences, Nagpur, India
8. King George's Medical University, Lucknow, India
9. Target Institute of Medical Education & Research, Mumbai, India, India
10. Medical Research Centre, Kasturba Health Society, Mumbai
11. Central Council for Research in Ayurvedic Sciences, New Delhi, India
Funding Statement: This study was funded by Central Council for Research in Ayurvedic
Sciences, Ministry of Ayush, Government of India.
Competing interests:
None of the authors have any financial conflict of interest regarding this
study. The authors Kuldeep Chuadhary, Alok Srivastava, Govind Reddy, Manohar Gundeti, BCS
Rao, Babita Yadav, Narayanam Srikanth work in Central Council for Research in Ayurvedic
Sciences (CCRAS), Ministry of AYUSH (MoA), Government of India (GOI), New Delhi. Dr
Ashwinikumar Raut was a consultant for the study. Dr Sanjay Tamoli was involved as a CRO.
AYUSH-64 is a proprietary formulation of CCRAS.
Contact Address:
Arvind Chopra, MD
Director and Chief Rheumatologist,
Centre for Rheumatic Diseases, Pune, India 411001
Telephone: +91 20 26345624, (M) 9822039297, Email: crdp5624@gmail.com
Key Words: COVID-19, Standard of Care, Ayurveda, Ayurvedic medicine, Herbal drugs,
Adjuvant therapy
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted June 17, 2021. ; https://doi.org/10.1101/2021.06.12.21258345doi: medRxiv preprint
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

2
ABSTRACT
Objectives: To compare the co-administration of an Ayurvedic drug AYUSH 64 as an adjunct to
standard of care (SOC) and SOC for efficacy and safety in the management of COVID-19.
Design: Multicentre, parallel efficacy, randomized, controlled, open label, assessor blind,
exploratory trial with a convenience sample. Patients followed to complete 12 weeks of study
duration.
Setting: COVID-19 dedicated non-intensive care wards at 1 government hospital, 1 medical
college teaching hospital and 1 medical university teaching hospital
Participants: 140 consenting, eligible, hospitalized adult patients suffering from mild and
moderate symptomatic COVID-19 and confirmed by a diagnostic (SARS-CoV-2) RT-PCR assay
on nasal and throat swab were randomized to SOC or SOC plus AYUSH 64. To be withdrawn if
disease becomes severe.
Interventions: Two tablets of AYUSH 64, 500 mg each, twice daily after meals, and continued
till study completion. SOC (symptomatic and supportive) as per national guidelines of India for
mild and moderate disease.
Main outcome measures: Time period to clinical recovery (CR) from randomization baseline
and proportion with CR within 28 days time frame; CR defined in the protocol
Results: 140 patients randomized (70 in each arm); 138 patients with CR qualified for analysis.
Both groups were matched at baseline. The mean time to CR from randomization was
significantly superior in AYUSH 64 group (95% CI -3.03 to 0.59 days); a higher proportion
(69.7%) in the first week (p=0.046, Chi-square). No significant differences observed for COVID-
19 related blood assays (such as D-Dimer). AYUSH 64 arm showed significant (p<0.05)
superior persistent improvement in general health, quality of life, fatigue, anxiety, stress, sleep
and other psychosocial metrics. 1 patient on SOC required critical care. 48 adverse events (AE)
reported in each group. Barring three SAE (in SOC), AE were mild and none were drug related.
22 participants (8 on AYUSH) were withdrawn. No deaths were reported.
Conclusions: AYUSH 64 hastened recovery, reduced hospitalization and improved overall
health in mild and moderate COVID-19 when co-administered with SOC under medical
supervision. It was safe and well tolerated. Further studies are warranted.
Trial registration: The Clinical Trials Registry India Number CTRI/2020/06/025557
Funding: CCRAS, Ministry of AYUSH, Government of India
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted June 17, 2021. ; https://doi.org/10.1101/2021.06.12.21258345doi: medRxiv preprint

3
INTRODUCTION
The world continues to reel under the tragic burden of the COVID-19 pandemic. The medical
system has been precariously overstretched and scarred. Several drug trials were completed and
many more are underway to unravel the evidence-based medicine (EBM) for more effective and
safe management (1). However, the treatment of mild- moderate COVID-19 remains empirical,
symptomatic and supportive (2, 3).
Several drugs were repurposed and extensively used for chemoprophylaxis and treatment of
COVID-19 (7). However, drugs such as hydroxychloroquine fell into disrepute because of lack
of clinical evidence (4). Despite limited evidence but based on good clinical experience, some
drugs such as tocilizumab continue to be used (5). Steroids became a pivotal treatment following
the result of a single large controlled drug trial (6).
The search to repurpose drugs (COVID-19) also rekindled vigorous research in the traditional,
complementary and alternative systems of medicine (TCAM) (8,9). TCAM and herbal medicines
in particular can be considered based on available data and clinical experience (10,11). It is now
known that the exuberant and dysregulated immune response in COVID-19 leads to life
threatening complications. Several medicinal plants from Ayurveda and traditional Chinese
medicines which are known to modulate immune response were considered as potential
therapeutic candidates (8, 12, 13, 14). Ayurvedic and other traditional herbal medicines are being
popularly used in India to prevent and treat COVID-19 since the beginning of the pandemic (15,
16, 17,18). Safety and tolerability of Ayurvedic herbal medicines could be an added advantage
for use in the community (19).
India has legal system to regulate and promote plural systems of medicine including Ayurveda,
Yoga, Naturopathy, Unani, Siddha, Sowa Rigpa and Homoeopathy, and together are known as
AYUSH systems. The Ministry of AYUSH (MoA) has established an Interdisciplinary AYUSH
Research and Development Task Force on COVID-19 to promote scientific research (20, 21).
Based on Ayurvedic logic and clinical experience, AYUSH-64 was considered for repurpose
therapeutic use in COVID-19. It is a standard proprietary poly-herbal formulation of Central
Council for Research in Ayurvedic Sciences (CCRAS) which was first developed in 1980 for the
treatment of Malaria (22). The current study aims to evaluate AYUSH 64 as an adjunct to
standard care in the treatment of COVID-19.
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted June 17, 2021. ; https://doi.org/10.1101/2021.06.12.21258345doi: medRxiv preprint

4
METHODS
This was a prospective, randomized, open label (assessor blind), two arm multicentre study with
an exploratory research design and was planned and carried out during the COVID-19 pandemic
(May-Nov 2020). The duration of study was 12 weeks. The study was carried out in the COVID-
19 dedicated non-intensive wards in the medical and teaching hospitals at King George Medical
University, Lucknow, Central Ayurveda Research Institute for Cancer, Mumbai and Datta
Meghe Institute of Medical Sciences, Nagpur. The study was carried out in accordance with the
principles of Good Clinical Practice (GCP), Declaration of Helsinki (Brazil update 2013), ICMR
(Indian Council of Medical Research) and MoA/CCRAS Guidelines (2018) (23, 24). The
protocol and the study report also complied with CONSORT guidelines (25). The protocol was
approved by the Institutional Ethics Committee at each study site and registered in the Clinical
Trials Registry of India (CTRI) (registration number CTRI/2020/06/025557) prior to patient
enrolment (26). The study was monitored by an independent data safety monitoring board and a
monitoring committee appointed by the sponsor. The overall scheme of the study, study
procedures and predetermined time points of evaluation are shown in Fig 1.
Patients
Voluntary hospitalized patients suffering from mild and moderate symptomatic COVID-19 were
selected and after signing informed consent were screened for eligibility. Patients were jointly
examined throughout the study by a modern medicine and Ayurveda physician (study
investigator). All patients were managed for COVID-19 by an attending physician designated by
the hospital at study site and who remained blinded to the treatment allocation in the trial
(assessor blind). Patients and study personnel were aware of the treatment allocation (open
label).
Adult patients with a typical clinical phenotype of COVID-19 illness and a laboratory
confirmation test for SARS-CoV-2 (RT-PCR on a nasal and/or throat swab) were selected.
Patients with severe symptomatic COVID-19 were excluded after fulfilling at least two criteria
(i) respiratory distress at room ambience (ii) Oxygen saturation (SpO
2
) at rest
≤
93% (iii) known
COVID-19 complication. Full details of the inclusion and exclusion criteria can be accessed in
the protocol registered at CTRI website (26).
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted June 17, 2021. ; https://doi.org/10.1101/2021.06.12.21258345doi: medRxiv preprint

5
Figure 1: Study Flow diagram showing Study Events and Timelines: A randomized controlled
study to evaluate the co-administration of AYUSH 64 with Standard of Care in COVID-19
Trial Procedures
Patients at each site were randomized to a SOC arm or AYUSH 64 (investigational product)
along with SOC (AYUSH plus) in 1:1 ratio on a first come first serve basis. A central
randomization schedule was prepared by a biostatistician (SS) using a standard statistical
Discharge
Baseline
Clinical Assessment
Diagnostic (RT-PCR), Routine
Haematology Profile, Special COVID-19
Assays, X-Ray Chest & Imaging, ECG
Randomize Eligible Patients
Screening of Consenting hospitalized patients suffering from Mild to Moderate COVID-19 for
Eligibility as per Inclusion-Exclusion Criteria
Medical History, Clinical Examination,
Ayurveda Assessment, Health Status
Time Points
Investigations
Week 4
Clinical Examination, Ayurveda
Assessment, Health Status, Adverse
Events
Routine Haematology Body Profile,
Special COVID-19 Assays
Week 8
Clinical Examination, Ayurveda
Assessment, Health Status, Adverse
Events
Routine Haematology Body Profile,
Special COVID-19 Assays
Week 12
Study Completion Assessment, Clinical
Examination, Ayurveda Assessment,
Health Status, Adverse Events
Routine Haematology Body Profile,
Special COVID-19 Assays
Assess Clinical Recovery, Ayurveda
Assessment; Health Status
Diagnostic (RT-PCR), Routine
Haematology Profile, Special Assays, X-
Ray Chest & Imaging, ECG
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted June 17, 2021. ; https://doi.org/10.1101/2021.06.12.21258345doi: medRxiv preprint

Frequently asked questions

Q1. What have the authors contributed in "Coadministration of ayush 64 as an adjunct to standard of care in mild and moderate covid-19: a randomised, controlled, multicentric clinical trial" ?

Ayurvedic drugs such as AYUSH-64 have been used in the treatment of COVID-19 pandemic this paper. 

Q2. What is the effect of AYUSH 64 on the patient?

It hastened clinical recovery, reduced hospitalization period and showed early persistent substantial benefit towards physical and mental health. 

Q3. How many patients were withdrawn from the study?

20 patients were withdrawn during the post recovery period; two patients with nonCOVID related SAE (malaria and diabetes with severe cellulitis), 1 patient with acute onset mild polyneuropathy and later diagnosed as Guillain Barre syndrome, and 17 patients who refused to continue in the study following hospital discharge. 

Q4. What is the purpose of the current study?

The current study repurposed a standardized Ayurvedic polyherbal formulation in popular Ayurveda (India) practise for over three decades to improve the efficacy of SOC treatment in COVID-19. 

Q5. What are the main reasons why AYUSH 64 is no longer favoured?

Several repurposed modern medicines (such as hydroxychloroquine and ivermectin) that were extensively used earlier in the pandemic are nolonger favoured (4, 7). 

Q6. What were the secondary efficacy measures for COVID19?

There were several secondary efficacy measures pertaining to (i) time lines such as mean duration from onset of symptoms to CR, mean duration from hospitalization to CR (ii) COVID19 related blood assay biomarkers such as C-reactive protein (CRP), D-Dimer, Ferritin, interleukin-6. 

Q7. What were the criteria for the inclusion of COVID-19?

Patients with severe symptomatic COVID-19 were excluded after fulfilling at least two criteria (i) respiratory distress at room ambience (ii) Oxygen saturation (SpO2) at rest ≤ 93% (iii) known COVID-19 complication. 

Q8. What software programs were used for intent-to-treat and per protocol analysis?

Standard statistical software programs were used (GraphPad InStat Version 3.6 and Confidence Interval Analysis software analysis, BMJ Group, London, 2003). 

Q9. What was the range of score shown in parenthesis?

The WHO QOL-BREF had 27 questions classified into 4 domains- physical health (Q 7-35), psychological health (Q 6-30), social relationships (Q 6-15) and environmental well- being (Q 8- 40); range of score shown in parenthesis. 

Q10. How many patients had co-existent diabetes or nave hyperglycaemia?

24% of the study cohort had co-existent diabetes or naïve hyperglycaemia on randomization which often required adjustment in blood sugar medication (Table 1). 

Q11. What was the symptomatic phenotype of COVID-19?

Adult patients with a typical clinical phenotype of COVID-19 illness and a laboratory confirmation test for SARS-CoV-2 (RT-PCR on a nasal and/or throat swab) were selected.