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CTRI Number  CTRI/2018/03/012418 [Registered on: 07/03/2018] Trial Registered Prospectively
Last Modified On: 12/11/2022
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Ayurveda 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Efficacy of Kashmaryadi Ghrita in reducing incidence of abortion 
Scientific Title of Study   Efficacy of Kashmaryadi Ghrita in reducing the incidence of Garbhasrava (abortion) : A randomized controlled clinical trial  
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Megha Gupta  
Designation  PhD Scholar 
Affiliation  IPGT and RA GAU Jamnagar 
Address  Department of Prasooti tantra avum Stree Roga IPGT and RA Gujarat Ayurved University Jamnagar
Department of Prasooti tantra avum Stree Roga IPGT and RA Gujarat Ayurved University Jamnagar
Jamnagar
GUJARAT
361008
India 
Phone  8627007980  
Fax    
Email  meghaguptaayu@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Prof Laxmipriya Dei 
Designation  Prof and HOD PTSR Deptt 
Affiliation  IPGT and RA GAU Jamnagar 
Address  5th Floor Room no 504 Department of Prasooti tantra avum Stree Roga IPGT and RA GAU Jamnagar
5th Floor Room no 504 Department of Prasooti tantra avum Stree Roga IPGT and RA GAU Jamnagar
Jamnagar
GUJARAT
361008
India 
Phone  9228198366  
Fax    
Email  deilaxmipriya@yahoo.com  
 
Details of Contact Person
Public Query
 
Name  Prof Laxmipriya Dei 
Designation  Prof and HOD PTSR Deptt 
Affiliation  IPGT and RA GAU Jamnagar 
Address  5th Floor Room no 504 Department of Prasooti tantra avum Stree Roga IPGT and RA GAU Jamnagar
5th Floor Room no 504 Department of Prasooti tantra avum Stree Roga IPGT and RA GAU Jamnagar
Jamnagar
GUJARAT
361008
India 
Phone  9228198366  
Fax    
Email  deilaxmipriya@yahoo.com  
 
Source of Monetary or Material Support  
IPGT and RA Gujarat Ayurved University Jamnagar 361008 
 
Primary Sponsor  
Name  INSTITUTE FOR POST GRADUATION TEACHING AND RESEARCH IN AYURVEDA 
Address  INSTITUTE FOR POST GRADUATION TEACHING AND RESEARCH IN AYURVEDA GUJARAT AYURVED UNIVERSITY JAMNAGAR GUJARAT 361008 
Type of Sponsor  Research institution and hospital 
 
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 
Megha Gupta   IPGT and RA Gujarat Ayurved University Jamnagar  OPD NO 12 PTSR Deptt IPGT and RA Gujarat Ayurved University Jamnagar Gujarat 361008
Jamnagar
GUJARAT 
8627007980

meghaguptaayu@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Ethics Committee IPGT and RA GAU Jamnagar  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  Married females in first trimester of pregnancy having history of 1 or more spontaneous abortions, (1) ICD-10 Condition:O200||Threatened abortion. Ayurveda Condition: GARBASRAVAH,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  GROUP A ORAL KASHMARYADI GHRITA   Kashmaryadi Ghrita 12 gm in two divided doses orally in morning and evening before meals with milk for 2 months  
Comparator Agent  GROUP B ORAL MICRONIZED PROGESTERONE  Micronized progesterone 200 mg orally twice a day with water after meals for 2 months  
 
Inclusion Criteria  
Age From  20.00 Year(s)
Age To  40.00 Year(s)
Gender  Female 
Details  Married females in first trimester of pregnancy having history of 1 or more spontaneous abortion Pregnancy of woman confirmed by urine pregnancy test and ultrasonography
 
 
ExclusionCriteria 
Details  Women in third trimester of pregnancy
Patients with severe systemic disease
cardiovascular complications diabetes mellitus
Diagnosed cases of disorders of reproductive tract like Tuberculosis Carcinoma Uterine fibroid Patients of incompetent os and congenital deformities of uterus Patients of STD like VDRL HIV
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   An Open list of random numbers 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Trial drug will help in continuation of pregnancy and also help in growth and development of fetus  18 months 
 
Secondary Outcome  
Outcome  TimePoints 
Drug may have effect in improving the minor ailments of first trimester of pregnancy  First trimester of pregnancy 
 
Target Sample Size   Total Sample Size="100"
Sample Size from India="100" 
Final Enrollment numbers achieved (Total)= "0"
Final Enrollment numbers achieved (India)="101" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)   26/03/2018 
Date of Study Completion (India) 03/03/2020 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="7"
Days="7" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details
Modification(s)  
1. Title - Pharmacognostical and Phyto chemical Standardization of Kashmaryadi Ghrita - A Herbal formulation for Recurrent abortion, Journal - World Journal of Pharmacy and Pharmaceutical Sciences, multidisciplinary monthly published, open access, peer reviewed,online pharmacy journal, Volume 7, Issue 11,2018, 1550-1559, ISSN 2278-4357, Impact factor - 7.421 2. Title - Management of Recurrent pregnancy loss and Subchorionic haemorrhage through Ayurveda with Kashmaryadi Ghrita:A case report, Journal - Journal ofAYUSH : Ayurveda,Yoga, Unani, Siddha & Homeopathy(STM journals), Volume 10, Issue 3,2021, 26-32, ISSN - 2321-6484 3. Title - Role of Pathya Apathya in preventing spontaneous abortion (Garbhasrava), Journal - International Journal of Research and Analytical Reviews, international peer reviewed & refereed , open access journal, Volume 8, Issue 4, 2021, 80-89, ISSN - 2349-5138, Impact factor - 7.17 
Individual Participant Data (IPD) Sharing Statement

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

Brief Summary
Modification(s)  

The research work entitled “Efficacy of Kashmaryadi Ghrita in reducing the incidence of Garbhasrava (abortion) : A randomized controlled clinical trial” was aimed to evaluate and compare the effect of Kashmaryadi Ghrita and micronized progesterone orally in reducing the incidence of Garbhasrava & to explore the etiopathogenesis of Garbhasrava in modern & Ayurvedic parlance. The study was undertaken keeping in view the present lifestyle, a main reason for abortion affecting a mother’s physical as well as emotional state. Moreover, to develop a standard Ayurvedic formulation to reduce the incidence of Garbhasrava, the present study was done. The trial was summarized in

1.      Introduction

2.     Conceptual study which includes Disease (Ayurvedic review & Modern review) and Drug review with Pharmacognostical & Pharmaceutical Study

3.     Clinical Study

4.     Discussion

5.     Summary & Conclusion.


HYPOTHESIS

NULL HYPOTHESIS (H0)

Kashmaryadi Ghrita is not as effective as micronized progesterone in reducing the incidence of Garbhasrava (abortion).

ALTERNATE HYPOTHESIS(H1)

Kashmaryadi Ghrita is equally or more effective than micronized progesterone in reducing the incidence of Garbhasrava (abortion).

STUDY DESIGN

Study type – Interventional

Intervention model – 2 Groups Assignment

Sample Size – 100 (50 in each Group)

Allocation (Method of randomization) - Computer generated randomization chart

Purpose -  Prevention

Masking - Open label

Timing - Prospective

End point – Efficacy & Safety

Introduction – In this part, a brief description regarding the topic Garbhasrava  with abortion in modern terms along with its prevalence, need & importance of the study, history of previous research works done, plan of study with aims & objectives, hypothesis and study design was mentioned in detail.

Conceptual Study – Disease Review 

Ayurvedic Review – In this part, the literature related to the Ayurvedic concept of abortion , Garbhasrava was explained in detail starting from the concept of Garbha in Ayurveda, essential factors mentioned for conception explained in different Ayurvedic texts, development of fetus , Garbhaposhana concept in Ayurveda, Monthwise development of fetus , various Garbhini Lakshana mentioned in Ayurveda after attaining pregnancy in terms of Sadyograhit Garbha and Vyakta Garbha Lakshana. Garbhasrava/ Garbhapata was detailed in terms of Paribhasha, Nidana, Samprapti, Lakshana and Chikitsa.

In Ayurveda , the word Garbhasrava and Garbhapata is used for abortion. Though the description of Garbhasrava is mentioned by different Acharyas, still the features of Garbhasrava are seen in various other diseases mentioned in Ayurveda like Yonivyapad, Jataharini, Shukradushti etc. So, all the causes of these diseases were also taken into consideration and treatment of these diseases could also be used according to the cause and described in the disease review. After collecting all the available mentioned literature regarding this, it was seen that the main Doshas responsible for Garbhasrava are Vata and Pitta.

Modern Review – It included the monthwise development of fetus according to modern science, description of abortion as its definition, etiology, Pathogenesis, detailed description of types of abortion along with its clinical features, differential diagnosis, investigations, complications & management, Recurrent abortion was explained in terms of etiology, diagnosis and management. At last, Sonography related details or parameters to assess growth and development of embryo or fetus in first trimester and then at 18-22 weeks was mentioned.

Drug Review – In this part of the study, description of the Ayurvedic trial formulation drug and modern drug selected and used for the study was mentioned in detail. Ayurvedic formulation details were mentioned with its each ingredient description and related researches.

Pharmacognostical study - Authenticity of the raw drugs of Kashmaryadi Ghrita was evaluated through pharmacognostical procedures. Organoleptic characters and powder microscopy of Kashmaryadi Ghrita ingredients was done as per the guidelines of Ayurvedic Pharmacopoeia of India.

Pharmaceutical study – The drug was analyzed using different physicochemical parameters and HPTLC profile of the drug was developed. All physicochemical parameters with HPTLC was under basic quality standards.

Clinical Study - The study was conducted by registering the patients fulfilling the inclusion criteria i.e. pregnant patients in first trimester (6-10 weeks) with history of spontaneous abortion, history of infertility, elderly primigravida, threatened abortion in present pregnancy into two groups- Group A & Group B. The patients were enrolled on the basis of computer generated randomization chart. 50 patients in Group A and 51 patients in Group B were registered for the study, being a total of 101 patients. In Group A, Kashmaryadi Ghrita was given orally in dose of 12 gms two times a day empty stomach wih a cup of cow milk for 2 months to pregnant women while in Group B, Micronized progesterone 200 mg twice a day with water orally after meals was given for 2 months to pregnant women. In both the groups, normal antenatal care protocol was advised to follow along with the drug. The patient was advised to come at 4 weeks interval and was advised Pathya Apathya with follow up at 18-20 weeks of pregnancy. All the patients were subjected to detailed history taking based on specially designed proforma and screened for Blood Group with Rh factor, HIV, HbsAg, VDRL before enrolment. Hb, TLC, DLC , ESR, Platelet count, PCV, Total RBC Count, BT, CT, FBS, LFT (Total Protein, S. albumin, S. globulin, SGOT, SGPT, Alkaline Phosphatase, S. Bilirubin), RFT (S. Urea, S.Creatinine) , S Cholesterol, Urine examination (Routine & Microscopic) , T4, TSH, S. Progesterone was carried out before & after treatment. T4 & TSH was repeated after treatment only in those patients who have abnormal report before treatment. TORCH test was done in selected patients. Ultrasonography was also done at first visit, at 11-13 weeks of pregnancy and at 18-20 weeks of pregnancy to detect any congenital anomaly.

Among 101 patients, 34 patients in Group A and 37 patients in Group B completed the course. 4 patients in Group A and 6 patients in Group B underwent abortion during the course of treatment. 12 patients in Group A and 8 in Group B could not complete the course due to their personal reasons and due to the prevailing corona virus condition at that time. Total 81 patients completed the study. Observations of all registered       patients (n=101) were included in the study and results of only those who have completed the study (n=81) were analyzed. The effect of the therapy was assessed on the basis of subjective parameters like continuation of pregnancy, relief in clinical features associated with Garbhasrava i.e. pain in lower abdomen and Bleeding Per vaginum, relief in minor ailments (associated features) of first trimester of pregnancy like Daurbalya, Aruchi, Nausea & Vomiting, Constipation, Pallor, Regurgitation & Heartburn, Palpitation, Shrama, Bhrama, Trishna, Katishoola & objective parameters like change in Serum Progesterone level and various diameters of embryo or fetus observed in Sonography. The observations were subjected to statistical evaluation to get the final results.

·       Out of total 81 registered patients, 71 patients i.e. 87.7% continued their pregnancy while 10 patients i.e. 12.3% of patients had abortion during course of treatment. In Group A, total 34 patients continued their pregnancy i.e. 89.5% of the patients of Group A while in Group B, 37 patients continued their pregnancy i.e. 86% of the patients of Group B while 4 patients in Group A i.e. 10.5% and 6 patients i.e. 14%  in Group B underwent abortion.

 

·        Out of total 34 patients who were TORCH positive, 26 patients i.e. 76.5% continued their pregnancy while 7 patients i.e. 20.6% of patients had abortion during course of treatment and 1 patient in Group A dropped out. In Group A, out of total 21 patients, 16 patients i.e. 80% continued their pregnancy and 4 patients i.e. 20% underwent abortion while in Group B, out of total 13 patients, 10 patients continued their pregnancy i.e. 76.9% and 3 patients i.e. 23.1%  in Group B underwent abortion.

Discussion – In this part, discussion was done on selection of topic, disease, drug, clinical study’s observations and results with effect of therapy. Probable mode of action of drug was also discussed in this part.

•        The trial drug Kashmaryadi Ghrita possess Garbhasthapaka, Rasayana, Raktapittashamaka and Raktastambhaka properties.

•        Pregnancy continuation seen in Group A is 89.5% while in Group B it is 86%.

•        Abortion in Group A is seen in 10.5% of cases while in Group B it was seen in 14%.

•        In cases of  TORCH positive patients, pregnancy was continued in 80% cases in Group A while continuation of pregnancy was seen in 76.9% in Group B and abortion was seen in 20% of cases in Group A while in Group B 23.1% cases result in abortion.

•        Moreover, on various blood & urine parameters, both Groups didn’t show any difference in results which are different from changes commonly seen during pregnancy.

•        So, it can be inferred that though statistically no significant results were found in both the groups in various parameters but clinically percentage wise Group A showed better results in pregnancy continuation and abortion than Group B.

So, the null hypothesis is rejected and alternate hypothesis is accepted. Kashmaryadi Ghrita is equally effective as micronized progesterone in reducing the incidence of Garbhasrava (abortion). 




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