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CTRI Number  CTRI/2017/12/010768 [Registered on: 06/12/2017] Trial Registered Retrospectively
Last Modified On: 22/05/2019
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Ayurveda 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Clinical study on Ayurine Plus Capsules Kidney stone 
Scientific Title of Study   A Randomized, Open Labeled, Multicenter, prospective, Clinical study to Evaluate efficacy and safety of AYURIN Plus Capsule in comparison with marketed Ayurvedic Formulation CYSTONE (Himalaya) in Urolithiasis" 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
AIRN/URO/2016 Version 1.0 Dated 26th Dec 2016  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Vijay P Ukhalkar 
Designation  Associate Professor  
Affiliation  Government Ayurveda College Vazirabad Nanded 
Address  Department of Shalya Tantra Government Ayurveda College Vazirabad Nanded

Nanded
MAHARASHTRA
431601
India 
Phone  9422171987  
Fax    
Email  ukhalkarvp@gmail.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Sanjay Tamoli 
Designation  Director 
Affiliation  Target Institute of Medical Education and Research 
Address  Target Institute of Medical Education and Research 205, B Wing, Blue Diamond Society, Nayagoan, Dahisar West, Mumbai

Mumbai (Suburban)
MAHARASHTRA
400068
India 
Phone  9322522252  
Fax    
Email  targetinstitute@yahoo.com  
 
Details of Contact Person
Public Query  
Name  Vandana Bade 
Designation  Manager - Clinical Trial Operation 
Affiliation  Target Institute of Medical Education and Research 
Address  Target Institute of Medical Education and Research 205, B Wing, Blue Diamond Society, Nayagoan, Dahisar West, Mumbai

Mumbai (Suburban)
MAHARASHTRA
400068
India 
Phone  8149507065  
Fax    
Email  vandana@targetinstitute.in  
 
Source of Monetary or Material Support  
Welex Laboratories Pvt Ltd. 1002, Marathon Innova Nextgen, Off Ganpatrao kadam marg, Lower Parel, Mumbai -400013 
 
Primary Sponsor  
Name  Welex Laboratories Pvt Ltd 
Address  1002, Marathon Innova Nextgen, Off Ganpatrao Kadam Marg, Lower Parel Mumbai -400013 
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 2  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Vijay P Ukhalkar  Government Ayurveda College Vazirabad Nanded   OPD No. 5, Ground Floor, Department of Shalya Tantra Vazirabad Nanded 431601
Nanded
MAHARASHTRA 		 9422171987

ukhalkarvp@gmail.com 
Dr Kamalakar Gajre  MAMs SS Ayurveda Mahavidyalaya and Sane Guruji Aarogya Kendra  Department of Shalya Tantra OPD No 3 Ground Floor,Malwadi Hadapsar Pune
Pune
MAHARASHTRA 		 9850123482

drgajarekv@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 3  
Name of Committee  Approval Status 
Institutional Ethics Committee Government Ayurvedic College and Hospital Nanded  Approved 
Institutional Ethics Committee, ASS Ayurved Mahavidyalaya, Nashik   Approved 
Institutional Review Board For Research, MAMs SS Ayurveda Mahavidyalaya and Sane Guruji Aarogya Kendra Malwadi Hadapsar Pune   Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  (1) ICD-10 Condition: N209||Urinary calculus, unspecified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  AYURINE Plus Capsules   Contains Trubulus Terrestris extract, Bergenia Ligulata extract, Crataeva Nurvala extract, Dolichos Biflorus, Boerhaavia Diffusa, Vetiveria Zizaniodes, Sida Cordifolia root extract , Hemidesmus Indicus, Asparagus Racemosus, Piper Cubeba Dosage and Treatment Duration: 2 Capsules of AYURINE Plus Twice a daily orally after food with water for 90 days.  
Comparator Agent  Marketed Formulation   Contains Didymocarpus pedicellata, Saxifaga ligulata, Rubia cordifolia, Cyperus scariosus, Achyranthes aspera,Onosma bracteatum, Vernonia cinerea, Purified, and Hajrul yahood bhasma Dosage and Treatment Duration: 2 tablets twice a day orally after food with water for 90 days 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  1.Patients having renal stone(s) greater than 05 mm and less than 12 mm in size.
2.Renal stone diagnosed by X-ray KUB and USG (abdomen and Pelvis).
3.Patients with or without symptoms such as hematuria, dysuria, pain in abdomen, and burning micturition.
4.Patient not taking any other lithotriptic agent.
5.Patient able and willing to give written informed consent and comply with the requirements of the study protocol.
6.Females of reproductive potential willing to use a reliable means of contraception (e.g. hormonal contraceptive patch, intrauterine device and physical barrier) throughout study participation.
 
 
ExclusionCriteria 
Details  1.Patients having acute renal colic.
2.Patients with stone in lower calyx.
3.Patients with moderate to severe uretero-hydronephrosis.
4.Complicated cases of Renal Calculi requiring surgical intervention.
5.Chronic renal failure.
6.Patients having clinically significant urinary tract infections.
7. Patients with known uncontrolled diabetes mellitus (DM), hypertension (HT), symptomatic congestive heart failure (CHF), unstable angina pectoris, myocardial infarction (MI).
8.Pregnant and breast feeding women.
9.Patients with clinically significant abnormal laboratory findings.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Not Applicable 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
1.Reduction in stone(s) size
2.Reduction in number of stones
 		 Day-3, Day 0, Day 15, Day 30, Day 45, Day 60, Day 75, Day 90 
 
Secondary Outcome  
Outcome  TimePoints 
1. Assessment of number of patients with complete expulsion of stone(s).
2. Assessment of duration (time) of expulsion of calculi.
3. Assessment of use of NSAIDs/ Anti-spasmodic drugs as rescue medicines.
4. Assessment of overall improvement in clinical symptoms :
5. Assessment of Drug Safety by assessing:
a. Adverse drug reaction.
b. Clinically significant Laboratory abnormalities.
 		 Day-3, Day 0, Day 15, Day 30, Day 45, Day 60, Day 75, Day 90 
 
Target Sample Size   Total Sample Size="72"
Sample Size from India="72" 
Final Enrollment numbers achieved (Total)= "62"
Final Enrollment numbers achieved (India)="62" 
Phase of Trial   Phase 2/ Phase 3 
Date of First Enrollment (India)   12/05/2017 
Date of Study Completion (India) 06/06/2018 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   Not Yet Done 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary
Modification(s)  		 Brief Methodology:

It is a Randomized, Open label, Multi-center, Prospective Clinical Study to evaluate efficacy and safety of AYURINE Plus Capsule in comparison with marketed Ayurvedic Formulation in Urolithiasis. The study will be conducted at two sites in India. Group A Subjects will be advised to take 2 Capsule of AYURINE Plus Twice a daily orally after food with water for 90 days. Group B Subjects will be advised to take 2 tablets of marketed formulation twice a day orally after food with water for 90 days. The primary objectives will be to evaluate changes in stone(s) size and reduction in number of stones. The secondary objectives will be to evaluate number of patients with complete expulsion of stone(s), duration (time) of required for expulsion of calculi, use of NSAIDs/ Anti-spasmodic drugs as rescue medicines, overall improvement in clinical symptoms, drug  Safety by assessing adverse drug reaction and clinically significant laboratory abnormalities

Results:

In the present study a total of 103 subjects were screened. There were 22 screen failures as they were not meeting the inclusion / exclusion criteria. Of these subjects, 81 subjects were randomized into two groups, 40 subjects in Ayurin Plus group and 41 in the Cystone group. A total of 19 subjects dropped out from the study. A total of 62 subjects (30 subjects in the Ayurin Plus group and 32 subjects in Cystone group) completed the study.

Age and Sex wise distribution of Subjects

The average age of subjects in the Ayurin Plus group was found to be 36.53 ± 10.58 years while in the Cystone group it was found to be 37.09 ± 11.92 years. There was no significant difference in the average age of subjects in the two study groups.

There were a total of 18 Males and 12 Females in Ayurin group while there were 20 Males and 12 Females in Cystone Group. In the Ayurin group there were 20 subjects who were in the age group of 18 to 40 years and in Cystone Group there were 19 subjects who were in this age group. 8 subjects in Ayurin group were in the age group of 41-50 years, 1 subject in the age group of 51-60 while 1 in the age group of 61-70 years. 8 subjects in the Cystone group were in the age group of 41-50 years, 5 subjects in the age group of 51-60 years.

Prakriti wise distribution:

In Ayurin group, there were 8 subjects of Vata-Pittaja and 2 subjects of Vata-Kaphaja Prakruti, 9 subjects of Kapha-Pittaja Prakruti, 5 subjects of Pitta-Kaphaja Prakruti and 6 subjects of Pitta-Vataja Prakruti. In Cystone group, there were 3 subjects of Vata-Kaphaja Prakruti, 4 subjects of Kapha-Pittaja Prakruti, 5 subjects of Pitta-Kaphaja Prakruti, 15 subjects of Pitta Vataja Prakruti and 5 subjects of Vata- Pittaja Prakruti.

Evaluation of effect on Renal Calculi

At the baseline visit, it was observed that in the Ayurin Group there were 46 calculi at baseline visit while at 45th Day and 90th Day the number of calculi reduced to 14 and 10 respectively i.e. 32 calculi were expelled by the 45th Day and 36 calculi were expelled by the 90th Day. In the Cystone Group 44 calculi were present at baseline which reduced to 23 at the end of day 45 and 13 at the end of 90 days i.e. 21 calculi expelled by the end of 45 days and 31 calculi expelled by the end of 90 days in this Group. There was a significant reduction in no of stones from baseline to day 45 and day 90 in both the groups. On analysis between the groups it was observed that Ayurin capsules showed a significant reduction in the no of stones at the end of 45 days.

Complete expulsion of Renal Calculi

Out of 30 subjects in the Ayurin Plus group, 21 (70%) subjects showed complete expulsion of renal calculi while in Cystone group out of 32 subjects, 19 (59.37%) subjects showed complete expulsion of renal calculi. When compared between the groups, the difference was statistically insignificant (p > 0.05).

Reduction in size of Renal calculi

At the baseline visit, the mean size of renal calculi was 6.55 ± 1.68 mm in Ayurin Plus group which reduced  to 5.93 ± 2.81 mm (p > 0.05) on day 45 and further reduced significantly (p < 0.05) to 4.5 ± 1.56 mm on day 90. At the baseline visit, the mean size of renal calculi in Cystone Group was 6.21 ± 1.47 mm which reduced to 5.88 ± 1.64 mm  (p > 0.05) on day 45 and 6 ± 1.77 mm at the end of the study (p > 0.05).

Evaluation of effect on Clinical symptoms

A)   Pain in abdomen

Pain in the abdomen due to real stone was assessed using VAS. In Ayurin Plus group, the mean abdominal pain score at baseline was 55.86 ±14.52, which reduced significantly to 25.55 ±21.81, 12±21.90 and 9.2±12.88 on day 30, day 60 and day 90 respectively. In Cystone group, the mean abdominal pain score at baseline was 53.43±18.94, which reduced significantly to 32.41±18.83, 14.8±20.43 and 15.93±19.15 on day 30, day 60 and day 90 respectively. When compared between the groups, the difference was statistically insignificant (p > 0.05).

B)   Number of pain episodes

At the baseline visit, the average numbers of abdominal pain episodes were 2.03 ± 1.48 in Ayurin Plus group, which reduced significantly (p < 0.05) to 0.20 ± 0.5, 0.157 ± 0.50 and 0.086 ± 0.288 on day 30, day 60 and day 90 respectively. At the baseline visit, the average numbers of abdominal pain episodes were 1.72 ± 1.19 in Cystone group, which reduced significantly (p < 0.05) to 0.40 ± 0.84, 0.16 ± 0.63 and 0.172 ± 0.468 on day 30, day 60 and day 90 respectively.  When compared between the groups, the difference was statistically insignificant (p > 0.05).

C) Other symptoms

At the baseline visit, 23 subjects were having burning micturition in Ayurin Plus group. The number of subjects having burning micturition was reduced to 9, 6 and 1 on day 30, day 60 and day 90 respectively. At the baseline visit, 22 subjects were having burning micturition in Cystone group. The number of subjects having burning micturition reduced to 9, 5 and 6 on day 30, day 60 and day 90 respectively.

At the baseline visit, 4 subjects were having hematuria in Ayurin Plus group. The number of subjects having hematuria reduced to 2, 0 and 0 on day 30, day 60 and day 90 respectively. At the baseline visit, 4 subjects were having hematuria in Cystone group. The number of subjects having hematuria reduced to 4, 3 and 2 on day 30, day 60 and day 90 respectively.

At the baseline visit, 12 subjects were having painful micturition in Ayurin Plus group. The number of subjects having painful micturition reduced to 4, 2 and 1 on day 30, day 60 and day 90 respectively. At the baseline visit, 22 subjects were having painful micturition in Cystone group. The number of subjects having painful micturition reduced to 4, 3 and 3 on day 30, day 60 and day 90 respectively. When compared between the groups, the difference was statistically insignificant (p > 0.05).

Requirement of rescue medicine

No subject of Ayurin Plus group required rescue medication like NSAID/Anti-spasmodic for management of pain in the abdomen, while 2 (6.25%) subjects from Cystone group required rescue medication at least once during the study period.

Assessment of safety (Vitals and Lab Parameter)

The vital parameters such as pulse rate, body temperature, respiratory rate, and blood pressure and laboratory investigations like mean renal profile, liver profile, lipid profile and CBC, ESR, Hb%, BSL-F were within normal limits both at the baseline visit and at the end of the study.

Adverse events

Out of 81 subjects, 36 were reported to have AE. In Ayurin Plus group, there were 30 adverse events (AEs) such as a cough, fever, nausea, insomnia, loose motion and hyperacidity during the trial. All the 30 AEs were unrelated to the study drug. In Cystone group, there were 39 adverse events (AEs) such as a cough, fever, nausea, insomnia, loose motion and hyperacidity during the trial. Among 39 AEs, 37 AEs were unrelated, while 2 were unlikely related to the study drug. No treatment or interruption of the study drug or procedure was required to resolve these episodes. Three was one SAE reported in the Ayurin Plus group. The SAE was reported to the IEC and was followed till complete resolution. SAE was not related to the study drug or procedure. The Majority of patients showed excellent tolerability to both the study drugs.


Conclusion:

The present study concludes that Ayurin capsules showed a significant reduction in both the number of stones and size over a period of 90 days of treatment. Marketed preparation (Cystone) though showed reduction in number of stones but size reduction was not found to be significant. On comparison between the two groups it was observed that Ayurin showed significant reduction in both number and size. 

 

A significant no of subjects also showed complete expulsion of stones in both the groups. Significant improvement was observed in the clinical symptoms in both the study groups.  

There was no significant change in the vitals in both the groups. The laboratory parameters for assessing the safety were found to be within normal limits at the end of the study signifying safety of consumption of the study products. Moreover none of the reported AE was serious and related to the study drugs.

It can be concluded form the present study that Ayurin plus is a safe and effective remedy in the management of Urolithiasis.


 
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