Clinical study on Ayurine Plus Capsules Kidney stone

Phase 2/3

Completed

Conditions: Urinary calculus, unspecified,

Registration Number: CTRI/2017/12/010768

Lead Sponsor: Welex Laboratories Pvt Ltd

Brief Summary: **Brief Methodology:**

It is a Randomized, Open label, Multi-center, ProspectiveClinical Study to evaluate efficacy and safety of AYURINE Plus Capsule incomparison with marketed Ayurvedic Formulation in Urolithiasis. The study willbe conducted at two sites in India. Group A Subjects will be advised to take 2Capsule 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 formulationtwice a day orally after food with water for 90 days. The primary objectiveswill 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 completeexpulsion of stone(s), duration (time) of required for expulsion of calculi,use of NSAIDs/ Anti-spasmodic drugs as rescue medicines, overall improvement inclinical symptoms, drug Safety by assessing adverse drug reaction andclinically 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 twogroups, 40 subjects in Ayurin Plusgroup and 41 in the Cystone group. A total of 19 subjects dropped out from thestudy. A total of 62 subjects (30 subjects in the Ayurin Plus group and 32subjects in Cystone group) completed the study.

**Ageand Sex wise distribution of Subjects**

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

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

**Prakriti wise distribution:**

InAyurin group, there were 8 subjects of Vata-Pittaja and 2 subjects ofVata-Kaphaja Prakruti, 9 subjects of Kapha-Pittaja Prakruti, 5 subjects ofPitta-Kaphaja Prakruti and 6 subjects of Pitta-Vataja Prakruti. In Cystonegroup, there were 3 subjects of Vata-Kaphaja Prakruti, 4 subjects ofKapha-Pittaja Prakruti, 5 subjects of Pitta-Kaphaja Prakruti, 15 subjects ofPitta Vataja Prakruti and 5 subjects of Vata- Pittaja Prakruti.

**Evaluation ofeffect on Renal Calculi**

At the baseline visit, it was observed that in the AyurinGroup there were 46 calculi at baseline visit while at 45th Day and90th Day the number of calculi reduced to 14 and 10 respectivelyi.e. 32 calculi were expelled by the 45th Day and 36 calculi wereexpelled by the 90th Day. In the Cystone Group 44 calculi werepresent at baseline which reduced to 23 at the end of day 45 and 13 at the endof 90 days i.e. 21 calculi expelled by the end of 45 days and 31 calculiexpelled by the end of 90 days in this Group. There was a significant reductionin no of stones from baseline to day 45 and day 90 in both the groups. Onanalysis between the groups it was observed that Ayurin capsules showed asignificant 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 outof 32 subjects, 19 (59.37%) subjects showed complete expulsion of renalcalculi. When compared between the groups, the difference was statisticallyinsignificant (p > 0.05).

**Reduction in size of Renal calculi**

At the baseline visit, the mean size of renal calculi was6.55 Â± 1.68 mm in Ayurin Plus group which reduced to 5.93 Â± 2.81 mm (p > 0.05) on day 45 andfurther reduced significantly (p < 0.05) to 4.5 Â± 1.56 mm on day 90. At the baselinevisit, the mean size of renal calculi in Cystone Group was 6.21 Â± 1.47 mm whichreduced to 5.88 Â± 1.64 mm (p > 0.05) onday 45 and 6 Â± 1.77 mm at the end of the study (p > 0.05).

**Evaluation of effecton 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 Â±14.52,which reduced significantly to 25.55 Â±21.81,12Â±21.90 and 9.2Â±12.88 on day 30, day 60 and day 90 respectively. In Cystonegroup, the mean abdominal pain score at baseline was 53.43Â±18.94, which reduced significantly to 32.41Â±18.83, 14.8Â±20.43 and15.93Â±19.15 on day 30, day 60 and day 90 respectively. When compared betweenthe groups, the difference was statistically insignificant (p > 0.05).

**B)** **Number of pain episodes**

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

**C) Other symptoms**

At the baseline visit, 23 subjectswere having burning micturition in Ayurin Plus group. The number of subjectshaving burning micturition was reduced to 9, 6and 1 on day 30, day 60 and day 90 respectively. At the baseline visit, 22 subjects were having burning micturition inCystone 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 subjectswere having hematuria in Ayurin Plus group. The number of subjects havinghematuria reduced to 2, 0 and 0 on day 30, day 60 and day 90respectively. At the baseline visit, 4subjects were having hematuria in Cystone group. The number of subjects havinghematuria reduced to 4, 3 and 2 on day 30, day 60 and day 90respectively.

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

**Requirement of rescue medicine**

No subject of Ayurin Plus grouprequired rescue medication like NSAID/Anti-spasmodic for management of pain in theabdomen, while 2 (6.25%) subjects from Cystone group required rescue medicationat 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 meanrenal profile, liver profile, lipid profile and CBC, ESR, Hb%, BSL-F werewithin 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. InAyurin Plus group, there were 30 adverse events (AEs) such as a cough, fever,nausea, insomnia, loose motion and hyperacidity during the trial. All the 30AEs were unrelated to the study drug. In Cystone group, there were 39 adverseevents (AEs) such as a cough, fever, nausea, insomnia, loose motion andhyperacidity during the trial. Among 39 AEs, 37 AEs were unrelated, while 2were unlikely related to the study drug. No treatment or interruption of thestudy drug or procedure was required to resolve these episodes. Three was oneSAE reported in the Ayurin Plus group. The SAE was reported to the IEC and wasfollowed till complete resolution. SAE was not related to the study drug orprocedure. The Majority of patients showed excellent tolerability to both thestudy drugs.

**Conclusion:**

The present studyconcludes that Ayurin capsules showed a significant reduction in both thenumber of stones and size over a period of 90 days of treatment. Marketedpreparation (Cystone) though showed reduction in number of stones but sizereduction was not found to be significant. On comparison between the two groupsit was observed that Ayurin showed significant reduction in both number and size. A significant no ofsubjects also showed complete expulsion of stones in both the groups.Significant improvement was observed in the clinical symptoms in both the studygroups. There was no significantchange in the vitals in both the groups. The laboratory parameters forassessing the safety were found to be within normal limits at the end of thestudy signifying safety of consumption of the study products. Moreover none ofthe reported AE was serious and related to the study drugs.

Itcan be concluded form the present study that Ayurin plus is a safe andeffective remedy in the management of Urolithiasis.

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 72

Inclusion Criteria

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.

Exclusion Criteria

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).
9.Patients with clinically significant abnormal laboratory findings.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1.Reduction in stone(s) size	Day-3, Day 0, Day 15, Day 30, Day 45, Day 60, Day 75, Day 90
2.Reduction in number of stones	Day-3, Day 0, Day 15, Day 30, Day 45, Day 60, Day 75, Day 90

Secondary Outcome Measures

Name	Time	Method
1.Assessment of number of patients with complete expulsion of stone(s).	2.Assessment of duration (time) of expulsion of calculi.

Trial Locations

Locations (2): Government Ayurveda College Vazirabad Nanded
🇮🇳
Nanded, MAHARASHTRA, India
MAMs SS Ayurveda Mahavidyalaya and Sane Guruji Aarogya Kendra
🇮🇳
Pune, MAHARASHTRA, India
Government Ayurveda College Vazirabad Nanded
🇮🇳Nanded, MAHARASHTRA, India
Dr Vijay P Ukhalkar
Principal investigator
9422171987
ukhalkarvp@gmail.com