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CTRI Number  CTRI/2020/06/025653 [Registered on: 05/06/2020] Trial Registered Prospectively
Last Modified On: 22/04/2024
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Ayurveda 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   A clinical trial to study the effect of local application of Apamarga Kshar Ointment in patients with internal haemorrhoid having complaints like bleeding through anus, some mass coming through anus 
Scientific Title of Study   Study of safety and efficacy of local application of Apamarga Kshar ointment in the management of Abhyantar Gudarsh with special reference to internal haemorrhoids. : Randomized Controlled Clinical Study 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Vipin Tryambakrao Tongale 
Designation  PhD Scholar 
Affiliation  Government Ayurveda College, Vazirabad, Nanded  
Address  Department of Shalya Tantra, Government Ayurved College, Vazirabad, Nanded Maharashtra

Nanded
MAHARASHTRA
431601
India 
Phone  9405404492  
Fax    
Email  dr.vipintongale@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Vijay P Ukhalkar 
Designation  Professor, Department of Shalya tantra 
Affiliation  Government Ayurveda College, Vazirabad, Nanded  
Address  Department of Shalya Tantra, Government Ayurved College, Vazirabad, Nanded Maharashtra
Department of Shalya Tantra, Government Ayurved College, Vazirabad, Nanded Maharashtra
Nanded
MAHARASHTRA
431601
India 
Phone  9405404492  
Fax    
Email  ukhalkarvp@yahoo.com  
 
Details of Contact Person
Public Query
 
Name  Vipin Tryambakrao Tongale 
Designation  PhD Scholar 
Affiliation  Government Ayurveda College, Vazirabad, Nanded  
Address  Department of Shalya Tantra, Government Ayurved College, Vazirabad, Nanded Maharashtra

Nanded
MAHARASHTRA
431601
India 
Phone  9405404492  
Fax    
Email  dr.vipintongale@gmail.com  
 
Source of Monetary or Material Support  
Dr Vipin Tryambakrao Tongale 
 
Primary Sponsor  
Name  Dr Vipin Tryambakrao Tongale 
Address  Konark Colony, Behind Rangoli Mangal Karyalaya, Kathora Road,Amravati 
Type of Sponsor  Other [Self for PhD Work] 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Vipin Tryambakrao Tongale  Government Ayurved College, Nanded  Department of Shalya Tantra Government Ayurved College Vazirabad nanded Maharashtra
Nanded
MAHARASHTRA 
9405404492

dr.vipintongale@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Ethics Committee, Government Ayurved Mahavidyalaya, Vazirabad, Nanded  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: K928||Other specified diseases of the digestive system,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Apamarga Kshar Pratisaran with Pathya  Once a week for 4 weeks Dosage – as required depending upon surface. Dosage schedule – After defecation in morning once a day. Route of administration - Topical (Locally on internal haemorrhoids) Procedure for local application Pratisarniya Kshar: Patient will be taken for local application after Hot sitz bath patient will be given lithotomy position. The Kshara karma will be performed with the help of slit type proctoscope under local anesthesia. Kshar wil be applied on internal hemorrhoids one after the other. After application on each hemorrhoid, the applied Kshara will be cleansed with lemon juice after changes in colour approx one to three minute. Yashtimadhu ghruta is applied over haemorrhoids. After that, a sterile pad kept at the anal verge to avoid soilage of clothes. Pathya ï‚· Hot sitz bath twice a day ï‚· Advice the patient to keep the local site hygienically clean. ï‚· Laxative – Avipattikar Churna 2-6 gm at bedtime with lukewarm water (Dose was adjusted as per requirement of patient. when constipation was not relieved dose may be increased). ï‚· Dietary control was advice. 
Intervention  Local Application of Apamarga Kshar Ointment with Pathya  Treatment of subject8 : Period Group A : Study Group - Once a daily for 4 weeks. Dosage for both groups – as required depending upon surface. Dosage schedule – After defecation in morning once a day. Route of administration - Topical (Locally on internal haemorrhoids) Procedure for local application of Apamarga Kshar ointment: Patient will be taken for local application after Hot sitz bath patient will be given lithotomy position i.e the patients is positioned supine comfortably with the knees flexed and abducted and buttocks projection well over the edge of table. The legs should be flexed at the hips and knees. Then local application at haemorrhoids will be applied. After that, a sterile pad kept at the anal verge to avoid soilage of clothes. Pathya ï‚· Hot sitz bath twice a day ï‚· Advice the patient to keep the local site hygienically clean. ï‚· Laxative – Avipattikar Churna 2-6 gm at bedtime with lukewarm water (Dose was adjusted as per requirement of patient. when constipation was not relieved dose may be increased). ï‚· Dietary control was advice. 
 
Inclusion Criteria  
Age From  21.00 Year(s)
Age To  70.00 Year(s)
Gender  Both 
Details  1) Patients having clinical symptoms of internal haemorrhoids
2) Patients of IInd and IIIrd degree internal haemorrhoids 
 
ExclusionCriteria 
Details  1) The patients of piles having previous history of haemorrhoidectomy.
2) Pregnant woman will not include in this study.
3) Patients taking other treatment from any pathy for the same problem during clinical trial.
4) Patients who are suspected of serious systemic disease i.e. DM, TB, malignancy, Syphilis or having portal obstruction
5) Patients Suspected of carcinoma of rectum, proctalgiafugax, chron’s disease, fistula in ano & where it is contraindicated
6) Patients with severe anaemia i.e haemoglobin less than 5 gm % 
 
Method of Generating Random Sequence   Coin toss, Lottery, toss of dice, shuffling cards etc 
Method of Concealment   Other 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Establishing Safety and efficacy of Apamarga Kshar Ointment in management of Internal haemorrhoids
 
4 weeks 
 
Secondary Outcome  
Outcome  TimePoints 
Reduction in symptoms of hemorrhoids, Size and degree of haemorrhoids
Cure of Disease 
4 weeks 
 
Target Sample Size   Total Sample Size="126"
Sample Size from India="126" 
Final Enrollment numbers achieved (Total)= "252"
Final Enrollment numbers achieved (India)="252" 
Phase of Trial   Phase 1/ Phase 2 
Date of First Enrollment (India)   01/07/2020 
Date of Study Completion (India) 05/10/2022 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="2"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Completed 
Recruitment Status of Trial (India)  Completed 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

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

Response - NO
Brief Summary
Modification(s)  

Hemorrhoids are a very common anorectal condition defined as the symptomatic enlargement and distal displacement of the normal anal cushions. Haemorrhoids, also called piles, are swollen veins in your anus and lower rectum; similar to varicose veins. Hemorrhoids have a number of causes, although often the cause is unknown. They may result from straining during bowel movements or from the increased pressure on these veins during pregnancy. Hemorrhoids may be located inside the rectum (internal hemorrhoids), or they may develop under the skin around the anus (external hemorrhoids). Worldwide, the overall prevalence of hemorrhoids in the general population is estimated to be 4.4%. It is estimated that more than 50% of the population over 50 years of age have experienced hemorrhoid problems13. It is very difficult to live with symptoms and complication of internal haemorrhoids. Anaemia due to per rectal bleeding secondary to haemorrhoids is one of important reason for blood transfusion. Multiple factors have been claimed to be the etiologies of hemorrhoidal development, including constipation and prolonged straining. The abnormal dilatation and distortion of the vascular channel, together with destructive changes in the supporting connective tissue within the anal cushion, is a paramount finding of hemorrhoidal disease.

Today’s lifestyle is changed; most of the people are not perfect in their food habits. They have bad food habits like irregular intake of food, eating of fried foods, excessive use of chilies and spices in food, etc. which is causative for haemorrhoids. Therapeutic treatment of hemorrhoids ranges from dietary and lifestyle modification to radical surgery, depending on degree and severity of symptoms. Those have their advantages and limitations. Variety of topical treatments is available in market. The primary objective of most topical treatment aims to control the symptoms rather than to cure the disease. Thus, other therapeutic treatments could be subsequently required. A number of topical preparations are available including creams and suppositories. These topical medications can contain various ingredients such as local anesthesia, corticosteroids, antibiotics and anti-inflammatory drugs4.

No radical topical treatment is not available. Hence radical non surgical treatment in form of topical ointment is need of time. After review of literature it was observed that such management of abhyantar Gudarsh is mentioned in ancient ayurvedic Samhita. Acording to Sushruta management of Abhynatar Gudarsh is of four types. Aushadhi Chikitsa, Ksharkarma, Agnikarma and Shastrakarma. Amongst that Ksharkarma is more effective non invasive method. Although effective but traditional Pratisaraniya Ksharkarma6 is more complex and tedious process. So modification in it is requirement of current era. 

Kshar Ointment is modification of Kshar Pratisaran. Previous study with Yava Kshar ointment was done. Siktha taila is previously used as a base for Kshar ointment preparation is proven safe and effective as a base.10 This showed encouraging results. But Yava Kshar is difficult to prepare and also expensive. Apamarga Kshar is used as Pratisaraniya Kshar at many places and is very effective7,8,9,10. Hence Apamarga Kshar is used in current study in place of Yava Kshar. Apamarga Kshar ointment which is an ointment of Apamarga Kshar with base Siktha taila is modified technique for Ksharkarma which will be used in current study.

Current Study is having novelty in selection of drug, drug dose and animal study. It is Open Labeled, Randomized Controlled Phase I/Phase II Clinical Study. Apamarga Kshar ointment will be prepared and tested with animal study for its effectiveness and its dermal safety. Animal Study will be carried out at Animal House of genuine institute. Clinical study will be carried out in two groups. Observation from both groups will be noted. Analyzed statistically and Discussed with conclusion after study.

 

Research Question

Whether Apamarga Kshar ointment is effective in Abhyantar Arsha Chikitsa to reduce per rectal bleeding and size of internal haemorrhoids?

 

Hypothesis

Hypothesis of this PhD thesis will be - Apamarga Kshar ointment applied locally at internal haemorrhoids once a day for 28 days with laxative ‘Avipattikar Churna’ orally is effective in reducing per rectal bleeding and degree of internal haemorrhoids.

H0 = Apamarga Kshar ointment applied locally at internal haemorrhoids once a day for 28 days with laxative ‘Avipattikar Churna’ orally is not effective in reducing per rectal bleeding and degree of internal haemorrhoids.

HA = Apamarga Kshar ointment applied locally at internal haemorrhoids once a day for 28 days with laxative ‘Avipattikar Churna’ orally is effective in reducing per rectal bleeding and degree of internal haemorrhoids.

 

Animal Study inference:

As per histopathological studies and hematological parameters, the application of Apamarga kshar ointment is effective in the management of croton oil-induced internal hemorrhoids in Wistar rats. It is not having any adverse effect on histopathology and in relation to hematological parameters. Increase in some lipid profile tests shows that Apamarga kshar ointment base was absorbed systemically but it did not have any negative changes on liver function test and kidney function tests. Hence, Apamarga kshar ointment can be used in humans for further clinical trials. 

 

Observation and results

Sexwise distribution of patients

It was observed that male and female patients were equally distributed in both group. A number of male patients was more than female patients in both groups. There is no significant statistical difference. Male patients were more than that of female patients. In previous studies, also it was observed that male patients are more than that of female patients133. However, in larger study it was found that males and females are equally affected by haemorrhoids134.

Agewise distribution of patients

Maximum patients in both group was from the age group 31 to 45 years and then between 45-60 years. This disease is more common in middle-aged people. In previous studies also it was mentioned that About 50% of people would have hemorrhoids at some point in their lives by the age of 50, and hemorrhoids affect 5% of the population on average at any given time.

Per rectal bleeding

It was observed that almost all patients were having either moderated or severe per rectal bleeding. When the clinical trial started, both groups were having equally distributed patients of per rectal bleeding. Bleeding is most common and important symptom of hemorrhoids, which takes patients to clinicians; hence, all patients were having per rectal bleeding before treatment. Per rectal bleeding was reduced with high significance with both treatments.

Apamarga kshar pratisaran is a trusted and proven treatment in the management of internal hemorrhoids. It reduces PR bleeding by inflammation, healing, and fibrosis of hemorrhoidal cushion.

Apamarga kshar ointment is used daily after defecation. It has all properties of Apamarga kshar, which is useful in reducing per-rectal bleeding after localized application. This action was supposed to be due to Apamarga kshar by producing inflammation and fibrosis of hemorrhoidal tissue. Base sikth taila is having lubricating properties, which help to lubricate and heal of hemorrhoidal cushion and reduce friction and injury to haemorrhoidal tissue while defecating and causing a reduction of per rectal bleeding.

Degree of Hemorrhoids

Patients with the degree of hemorrhoids grade II and grade III were present in both groups. Both groups are having no statistical difference in a baseline. Maximum patients were from grade II and grade III. Many patients ignore symptoms in grade I and in Grade IV surgery is the choice of treatment.135 Hence, for conservative treatment only grade II and grade III patients were available and selected as inclusion criteria for study.

With both treatments, change in the degree of hemorrhoids was observed late i.e. after 28 days to 45 days. This change may be observed due to the healing and fibrosis of hemorrhoidal tissue, which ultimately reduces prolapsing mass. Long-term follow-ups and treatment may change the degree of hemorrhoids in many patients. This needs further prolonged study. Over all treatment was effective with high significance in reduction of prolapse mass of hemorrhoids and degree of hemorrhoids.

Discharge per anal

It was observed that discharge per anal was mild in maximum patients at the beginning of the study and difference in both group was not significant. Hence, both groups were from the same population.

Discharge per anal is maximum and associated with patient having 4th grade hemorrhoid. In the current study, the maximum patient was from 2nd Grade and 3rd Grade. Hence a maximum number of patients were with mild to nil discharge per anal. After treatment in a group, reduction in per anal discharge was seen in both groups. Overall treatment was effective in treatment of discharge per anal.

Final Outcome:

Primary Outcome:

It was observed that all patients from both groups has improvement in disease. Per rectal bleeding was totally stopped in 101 (92.66%) and 102 (95.32%) patients in Apamarga kshar pratisaran and Apamarga kshar ointment group respectively. Per rectal bleeding reduced to mild in 8 (7.32%) and 5 (4.67%) patients in Apamarga kshar pratisaran and Apamarga kshar ointment group respectively. Discharge per anal totally stopped in 105 (96.33%) and 102 (95.32%) patients in Apamarga kshar pratisaran and Apamarga kshar ointment group respectively

Discharge per anal was reduced to mild in 2 (2.75%) and 4 (3.74%) patients in Apamarga kshar pratisaran and Apamarga kshar ointment group respectively. Change in degree of hemorrhoids observed in 32(25%) patients treated with Apamarga kshar pratisaran and 26 (21%) patients treated with Apamarga kshar ointment.

All patients who underwent complete treatment have shown improvement in both groups.

19 (15%) patients from Apamarga kshar ointment group and 17 (13.49%) patients from Apamarga kshar pratisaran group dropped out as they did not completed treatment protocol.

No complete cure in any patient of both groups was observed.

Secondary Outcome:

No complication observed in any groups. Initially local irritation observed in some patients who did not wipe anal region after treatment. However, it was resolved after 2 to 3 days of taking care about wipe out excessive ointment at anal region. 

Conclusion

From results and statistical analysis, it was concluded that

Apamarga kshar ointment applied locally is effective in reducing C reactive protein significantly as compared to active control. It has histopathological changes indicating reduction in inflammation, healing with fibrosis. It reduces recto anal coefficient after treatment as compared to active control.

Application of Apamarga kshar ointment is effective in management of croton oil induced internal hemorrhoids in Wistar rats.

Apamarga kshar ointment was absorbed in systemic circulation and showed minimal increase in serum triglycerides, serum LDL and VLDL cholesterol. However, it did not have any negative effect with respect to liver function test and Kidney function test of Wistar rats. Hence, Apamarga kshar ointment is safe and not having any acute toxic effect.

Primary Outcome : Apamarga kshar ointment reduced per rectal bleeding from 3rd day and it was nil in 95.66% compared to Apamarga kshar pratisaran, in which it was 92.06% patients after 28 days.

Apamarga kshar ointment was effective in reduction of degree of internal hemorrhoids in few patients but it did not reduced degree of haemorrhoids in all patients. Long-term treatment may be effective in reduction of degree of internal hemorrhoids.

Apamarga kshar ointment was effective in reduction of per anal discharge associated with internal hemorrhoids nil in 95.33% compared to Apamarga kshar pratisaran, in which it was 96.33% patients after 28 days.

Secondary Outcome : No complications was observed with treatment.

Hence, It is concluded that Apamarga kshar ointment is effective in management of per rectal bleeding, reducing per anal discharge due to internal hemorrhoids and degree of hemorrhoids up to some extent.

Thus, alternative hypothesis HA i.e. Local application of Apamarga kshar ointment at internal haemorrhoids once a day for 28 days with laxative ‘Avipattikar Churna’ orally is effective to reduce per rectal bleeding and gradation of internal haemorrhoids is accepted

 

Difficulties in actual work :

Local application of Apamarga kshar ointment is to be done by patient at home. Therefore, application of ointment has possible error due to improper technique by patient, not following proper treatment schedule and protocol by patient.

If some part of ointment remains on normal skin then it can cause local irritation and excoriation. Hence, patient must be advised to wipe out extra ointment, which is present outside of anus.

Squeezing pressure by patient can differ much time. Hence, quantity of ointment applied at hemorrhoids differs and which can interfere with desired outcome.

Ointment base is sikth taila, which is combination of Tila taila and beeswax it tends to get harder in consistency during winter. This makes application of ointment difficult as ointment come out of tubes difficultly and only after excessive pressure. This problem was tackled by advising patient to keep ointment tube in warm water before application. Further, by increasing proportion of Tila taila in base sikth taila this problem can be solved.

Use of slit proctoscope is sometimes painful. While removing proctoscope if slit proctoscope is not having complete slit then hemorrhoid gets stuck in lower end of proctoscope and it hurts patient.

If slit is complete then obturator of proctoscope does not fix properly and again it may hurt patient while insertion of proctoscope. Hence, procedure should be done very delicately and with well-lubricated proctoscope only.

Apamarga kshar pratisaran need one or two assistant while applying kshar. One assistant is required for holding proctoscope and another for providing kshar, Amla dravya and other instruments.

Application of Apamarga kshar can be done with spatula. Loss of drug i.e. Apamarga kshar is observed if pratisaran is done with the ear buds or cotton swabs.

Assessment of per-rectal bleeding, discharge per anal and prolapsed of hemorrhoid during defecation is totally dependent on patients response. It is not possible for assessment actually by intervening doctor. This error can cause error in final interpretation.

 

Suggestions

Long-term comparative animal study i.e. for full duration of treatment is expected to be done for assessment of local changes after long-term treatment.

Assessment of changes in lipid profile of animals after long-term treatment and after seasation of treatment for one month.

Study for longer duration for assessment of complete reduction in degree of hemorrhoids.

Study for changes in lipid profile of patient using Apamarga Kshar Ointment,

 


 
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