A study to compare the efficacy of ayurvedic intervention with the conventional intervention in management of episiotomy wound- a non-inferiority open labelled randomized clinical trial

SYNOPSIS FOR MS (Ayu.) DISSERTATION

A STUDY TO COMPARE THE EFFICACY OF AYURVEDIC INTERVENTION WITH THE CONVENTIONAL INTERVENTION IN MANAGEMENT OF EPISIOTOMY WOUND- A NON-INFERIORITY OPEN LABELLED RANDOMIZED CLINICAL TRIAL

 

   Name of Scholar

 Dr. Sanika Sanjay Aphale

GUIDE                                                           CO-GUIDE                                           CO-GUIDE

Dr. Swati V. Gaikwad                        Prof. Dr. Sujata D. Kadam              Dr. Ruchi Arora

Associate professor                            Professor and head,                             Counsultant

Dept of  PTSR                                    Dept of PTSR                                     Dept of  PTSR

AIIA , New Delhi                               AIIA , New Delhi                             AIIA , New Delhi

DEPARTMENT OF STREE ROGA AND PRASUTI TANTRA

ALL INDIA INSTITUTE OF AYURVED, NEW DELHI

**(**An autonomous organisation under the Ministry of Ayush, Govt of India)

             Gautampuri, Saritavihar, New Delhi -110076

Batch -2023-2026                                                                                              Enrollment no-  23AIIAMMAM000023

CERTIFICATE

This is to certify that DR. SANIKA SANJAY APHALE, first year PG. (Ayu.) Scholar in the department of prasuti tantra evam stree roga, All India Institute of Ayurveda,

New Delhi has proposed her dissertation entitled

“A STUDY TO COMPARE THE EFFICACY OF AYURVEDIC INTERVENTION WITH THE CONVENTIONAL INTERVENTION IN MANAGEMENT OF EPISIOTOMY WOUND- A NON-INFERIORITY OPEN LABELLED RANDOMIZED CLINICAL TRIAL**’**’who is a bonafide student of this  Institute of 2023-2026 Batch.

 (PROF.) DR. TANUJA NESARI

Director

All India Institute of Ayurveda

Date:

Place: New Delhi

 TITLE:

A study to compare the efficacy of ayurvedic intervention with the conventional intervention in management of episiotomy wound- a non-inferiority open labelled randomized clinical trial

RESEARCH QUESTION :

Whether there is a difference in efficacy in the management of episiotomy wound by ayurvedic and conventional interventions?

 NULL HYPOTHESIS :

Ayurvedic intervention is not equally effective than the conventional intervention in the management of episiotomy wound

ALTERNATE HYPOTHESIS :

Efficacy of Ayurvedic intervention is not-inferior to that of the conventional intervention in the management of episiotomy wound

    Introduction:

The disease burden of puerperal sepsis and its association with maternal mortality is of a great concern. It accounts for 11% of maternal mortality globally[1]On the other hand, WHO states that the world is running out of antibioticsand  dedicates the theme for world health day as ‘‘Antimicrobial resistance:no action today ,no cure tomorrow’’ way back in 2011. Ayurveda has a great potential to not only prevent the incidences of puerperal sepsis post normal vaginal deliveries but also holistically aid the smooth transition of puerpera and can in turn contribute effectively in reducing this crisis of antimicrobial resistance.

            Contemporary Review:

Puerperium is a period following the child birth during which the anatomical organs and the physiology of body returns back to pre-pregnant state. The period of puerperium begins after the expulsion of placenta till 6 weeks when the uterus regresses to non-pregnant size.

It is a state of low immunity due to wounds, lacerations in cervix,vagina,placental site and blood loss. The presence of a variety of microorganisms in vagina eg staphylococcus, e coli, clostridium,yeasts etc are likely to become virulent in this situation owning to lowered immunity. In India, it is a common practice to give antibiotics after episiotomy as prophylaxis ,maybe due to hygiene concerns.

Episiotomy is a surgically planned incision taken on the perinium to facilitate the birth of the child during a vaginal delivery. There has been a controversy regarding usage of systemic antibiotics as prophylaxis for normal vaginal delivery episiotomy ( 2nd degree perineal tear)[2,4]. While some textbooks recommend the use of systemic antibiotics as prohylaxis in normal vaginal delivery episiotomy ( 2nd degree perineal tear) others don’t.  As per WHO guidelines oral antibiotics are not recommended in episiotomy .As per ACOG practice bulletin, antibiotics are only indicated in 3rd and 4th degree perineal tear.The DC Dutta textbook of obstetrics recommend the use of local antibiotic ointment along with oral analgesics but do not mention the use of systemic antibiotics[3]

 Administration of antibiotics may have adverse effect on both mother and the child. As a well-known fact the use of antibiotics causes a disturbance in the gut microbial flora which can lead to IBS , hormonal imbalances , metabolic diseases[7]. It also induces resistance to the antibiotics. The use of antibiotics in the mother decreases breast milk secretion and it also kills the good bacterias in vagina which leads to vaginosis of the puerperium.[5]

Some antibiotics which are relatively safe during lactation are penicillins,clavulanic acids,cephalosporins,metronidazole at low doses . Analgesics like paracetamol , low dose aspirin are also considered compatable with breast feeding. [9]

Classical review

Episiotomy according to ayurved is Sudha chinna vrana which will follow the principals of vrana chikitsa for its management.[6]

Sutika, as described in the classics is a female who has delivered a baby. Sutika kaal is considered to be of 6 weeks Sushrut[7], ashtang hriday[8]  alternatively till the women starts menstruating, while kashyap mentions a period of 6 months[9] , as this period is required by the female to gain back the physiological state of the body.

Sutika Avastha is a very fragile condition because her body is emaciated due to development of the fetus and also empty due to blood loss during delivery , vitiation of vaatdue to labour pains. Any disease in this condition would lead to the diseases that are very difficulty to cure, so all the samhitas have mentioned paricharya to avoid this from happening.

Thus the management of episiotomy wound in sutika avastha will require certain modifications in the treatment protocols mentioned in classics considering this physiological state. The classics expect vaidyas to use yukti Pramana to address this.

 Review of previous works:

                         

Sr
no

Study title

Author

Drugs / methods used

Knowledge gap

|1.

Validation of the effect of an ayurvedic therapeutic procedure, Dashmoolkwath and dhoopan – fumigation with medicinal herbs during first week of puerperium- an open clinical trial[10]

Dr Seema R. Gholap

DR N. V. khairnar

Dashmool kwath,

yoni dhoopana with kushta, aguru,guggulu

1)Specificity of antimicrobial action of dhoopana dravyas used not mentioned

Details about dhoopana upakrama regading the length of dhoopana tube , distance from the opening of tube from the wound,temperature of dhoopana  not mentioned

REEDA SCALE for episiotomy wound healing not used

  |2

Determining the efficacy of combination of three ayurvedic formulations and dhoopana in prevention of infections post vaginal delivery with episiotomy[11]

Dr Swati Mohite

Vidanga, shatapushpa,jatamansi, guggulu sprinkled on embers  and dhoopana done with the fumes.

Balant kadha

Saubhagya shunthi paak

Shatavari kalpa

1)REEDA SCALE for episiotomy wound healing not used

2)Specificity of antimicrobial action of dhoopana dravyas used not mentioned

3)standardization regarding temperature of dhoopana not done

  |3

Clinical efficacy of local guggulu dhoopana in management of episiotomy wound[12]

Dr Garthe limbanappa Somnath

Dr Ravikiran Ram Bhosale

Ghrita and guggulu dhoopana

1)laboratory investigations not done to support the clinical findings

|4

Evaluation of Dhoopana karma in sutika paricharya[13]

Dr Vidyaa Maruti Magar

Dr S R Gholap

Kushta ,aguru,guggulu

dhoopana

Specificity of antimicrobial action of dhoopana dravyas used not mentioned

|

 Need of research :

 1.     The research work done previously show that episiotomy can be managed by ayurvedic regimen but the spectrum of antimicrobial action is not mentioned clearly.

2.     If ayurvedic regimen has to be implemented in episiotomy wound management, more RCTs taking antibiotics as the comparator group is needed in order to have a thorough comparative analysis

 Primary objectives:

.To study the efficacy ofayurvedic intervention in episiotomy wound management and compare its effectiveness with the conventional intervention.

Secondary objectives:

1.    To assess the effect of yoni dhoopana on lochia

2.    To assess in-vivo antimicrobial action of the formulations used

3.    To examine the possible mode of action of the upakrama and dravyas used

4.    To examine adverse effects if any

Outcome measures:

PRIMARY OUTCOME:

1)     Healing of episiotomy wound

 SECONDARY OUTCOME:

Reduction in the colony count of bacterias

Decrease in pH of lochia

 Materials and methods

Plan of Study-

1)    Literature review-

-        Drug Review

-        Episiotomy Wound healing Review

2)     Pharmaceutical review-

-        Procurement of RAW material

-        Identification and authentication of Raw drugs

3)    Clinical study

 Drug review:

Triphala guggulu – will be procured from GMP certified pharmacy

अथ त्रिफला गुग्गुलुर्भगन्दरादौ –

त्रिपक्षं त्रिफलाचूर्णं  à¤•à¥ƒà¤·à¥à¤£à¤¾à¤šà¥‚र्णं पलोन्मितम् ।

गुग्गुलुं पाञ्चपलिकं क्षोदयेत्सर्वमेकतः ॥ ८२ ॥

ततस्तु गुटिकां कृत्वा प्रयुञ्ज्याद्वन्ह्यपेक्षया ।

भगन्दरं गुल्मशोथाव**र्शां**सि च विनाशयेत् ॥ ८३ ॥

( शा.सां.म.खां.82-83 )

     

Sr no

Name of ingredient

Latin name

family

Part used

|1

Haritaki

Terminalia chebula Retz.

Combretaceae

Fruit

|2

Amalaki

Phyllanthus emblica L.

Euphorbiaceae

Fruit

|3

Bibhitaki

Terminalia bellirica Retz.

Combretaceae

Fruit

|4

Pippali

Piper longum linn.

piparaceae

Fruit

|5

Guggulu

Commiphora wightii Linn.

Burseraceae

Resin

|

    Dhoopan Dravya :

Sr no

Name of ingredient

Latin name

Family

Parts used

|1

Sarjarasa

Vateria indica Linn

Dipterocarpaceae

Resin

 Procurement :The drug will be procured from the market

Authentication: The drug will be authenticated from Pharmacognosy lab, AIIA, New Delhi

     Jatyadi Tail: will be procured from GMP certified pharmacy

जातीननम्बपटोलानाां नक्तमालस्य पल्लवााः ।। 168 ।।

नसक्थांसमधुकां कुष्ठां द्रेननशेकटुरोनहणी ।

पद्मकां लोध्रमभया नीलमुत्पलम्।। 169।।

तुत्थकां साररवा बीजांनक्तमालस्य दापयेत्।

एतानन समभागानन नपष्ट्वा तलैनवपाचयेत्।। 170।।

नाडीव्रणेसमुत्पन्नेस्फोटकेकच्छुरोनगषु।

सद्याः शस्त्रप्रहारेषुदग्धनवद्धेषुचव नह ।।  171 ।।

नखदन्तक्षतेदेहेव्रणेदुष्टेप्रशस्यते। (शा.सां.म.खां. 9/168-17)

    Contents of Jatyadi Tail

    STUDY DESIGN- Open labelled randomized clinical trial

STUDY TYPE- Interventional

TIMING- Prospective

DURATION-7 days

DRUG FREE FOLLOW UP-14th,45th day after vaginal delivery

END POINT- Healing of episiotomy wound

SAMPLE SIZE- 60 ( 30 in each group )

RANDOMIZATION:  Variable Block Randomization

  Plan of study:

Time- Within 24hrs of Normal vaginal delivery

Treatment plan :  A) Internal Medication

B) local treatment

A)   Internal Medication- Tablet triphala guggulu 500mg twice a day before food

 B)    Local treatment – The following treatment will be done twice a day for 5 days

 STANDARD OPERATIVE PROCEDURE  FOR DHOOPANA-

{ To be done twice daily at the interval of 10-12 hrs}

Patient is asked to evacuate the bladder and bowel before therapy

Cleaning the episiotomy wound with Sterile water in lithotomy position and drying it

New disposable sheets will be used for every patient on each day of dhoopana

                         5gm of sarjarasa powder will be sprinkled on 75gm of red hot charcoal with 5ml of

ghee  in a mud pot  (shaarav)  until sufficient quantity of fumes are created

    Patient is made to sit on a wooden chair having diameter of approximately 30cm

such that  the episiotomy wound on the perineum is exposed to the fumes.

The distance of perineum will be approximately about

50cm ( janu tulya aasan ) from the upper border of shaarav

Dhoopanawill be done for 5-7 mins

        STANDARD OPERATIVE PROCEDURE FOR APPLICATION OF JATYADI TAIL:

{ To be done twice daily at the interval of 10-12 hrs}

After the dhoopana, patient will be given lithotomy position

   Autoclaved jatyadi oil will be taken on a gauze in sufficient quantity according to the size of wound ( approximately 15-20 ml)

   The gauze will be placed over the episiotomy wound and will be removed after 5 mins.

                          

GroupA

(Control group)

Tb Cefuroxime and clavulanic acid twice a day

Tb Aceclofenac 100mg+ Paracetamol 325mg+ Serratiopeptidase 15mg three times a day

Betadine ointment and solution for local application

|Group B

(Trial group)

Yoni Dhoopan with sarjarasa, local application of jatyadi tail done twice daily and tb triphala guggulu 500mg twice a day before food

Drug Delivery Regimen:

 

GROUP

DRUG

ROUTE AND DOSE OF ADMINISTRATION

DURATION

|A

Tb Cefuroxime and clavulanic acid

Oral – twice a day- after food with water

5

| Tb Tb Aceclofenac 100mg+ Paracetamol 325mg+ Serratiopeptidase 15mg

Oral – twice a day- after food with water

7

| Betadine solution and ointment

Local – As per size of episiotomy

7

| Tb Triphala guggulu 500mg

Oral – twice a day- after food with water

7

|B

Sarjarasa dhoopana

Local – As per size of episiotomy

5

| Jatyadi tail

Local – As per size of episiotomy

7

 **Duration of trail –**7 days

 **Follow up period –**14th , 45th days

 sample size  --

As per the practices at AIIA, we have seen at least 90% success rate in achieving complete wound healing, where as pervious clinical trials suggest 85% success rate in achieving complete wound healing using ayurvedic intervention. However, we wish to explore if ayurvedic intervention can replace the conventional intervention. Therefore, a non-inferiority clinical trial is being conducted. It is assumed that the proposed ayurvedic intervention may help to achieve complete healing in 85% of cases, assuming 10% non-inferiority margin, 80% power , 5% level of significance

The calculated sample size in each group is 60 (67 with 10% drop out)

Due to time constraint, the sample size will be taken as 60 (30 in each group)

    Enrollment Of Patients:

All the patients will be enrolled from Labour room and ANC OPD of All India Institute of Ayurved, New Delhi.

Inclusion criteria:

1.     Patients of age group 20-40 years of age

2.     Patients with normal vaginal delivery with episiotomy( 2nd degree perineal tear)

ICD 11:

ICD 11 code for episiotomy is JB44.1- Disruption of perineal obstetric wound

The following synonyms will be excluded –

-        Obstetrical breakdown of perineum

-        Disruption of perineal laceration repair in puerperium

-        Wound dehiscence

Exclusion criteria:

1. Post operative LSCS patients
2. Patients having asthma, COPD, dust allergies
3. Patient having 3rd and 4th degree tear,

paraurethral tear

4.  Patient with DM, severe anemia[hb<8gm/dl],   other immunocompromised conditions.

5.  Patients with vaginosis , vaginitis, cervicitis or PID

6.   Breast abscess, mastitis

7.   Patients not willing to participate

 Investigations before treatment:

CBC with ESR,

APTT,PTINR,

LFT,KFT,

RBS F, RBS-PP,

URINE Routine -Microscopy,

HIV ANTIBODY 1 and 2,

Anti HCV,

HBsAG,  VDRL.

          Parameters for assessment :

   A.    PAIN SCALE-  ( assessed on 0,1,2,3,4,5 days post-NVD) [14]

 

   B.    CBC WITH ESR(0th ,5th day)

 C.Swab culture(0th ,5th day)

 D.ph of lochia(0th to 5th day post NVD)

 E.REEDA CRITERIA-(0th, 3rd,5th)[15]

F. Quantity of Lochia-( 7 consecutive days post NVD )[16]

       

Points

Redness

Edema

Ecchymosis

Discharge

approximation

|0

None

None

None

None

Closed

|1

<0.25cm of incision bilaterally

<1cm from incision

<0.25cm bilaterally or 0.5cm unilaterally of incision

serous

Skin separation <3mm

|2

<0.5cm of incision bilaterally

1-2cm from incision

<0.25cm-1cm bilaterally or 0.5cm-2cm unilaterally of incision

serosanguinous

Skin and subcutaneous fat separation

|3

0.25cm of incision bilaterally

2 from incision or affects vulvar area

1cm bilaterally or 2cm unilaterally of incision

Bloody purulent

Skin and subcutaneous fat separation

Healed :0             Moderately healed:1-5                  Mildly Healed :6-10        Not healed:11-15

       

DAYS

     PARAMETERS

0th day

3rd day

5th day

|REEDA

     |WBC COUNT

  -------------

  |ESR COUNT

  --------------

Table : assessment parameters

   

PARAMETERS

     DAYS

 PAIN

pH   of LOCHIA

 PADS STAINED PER DAY

(280mm) with nature of discharge

  |Before dhoopana

After dhoopana

Before dhoopana

After

dhoopana

Involution of uterus below umbilicus

|0

         |1

         |2

         |3

         |4

          |5

         |

Table : assessment parameters

   Assessment of result:

· The data would be presented in the form of Descriptive Statistics such as Mean ± SD, SEM or Range etc., whichever is applicable. The data would be depicted in the form of Tables, Charts, Graphs, Diagrams etc., wherever it is applicable.  Data related to all the intend to treat participants would be considered for safety related assessments and those completing the course of treatment (Per protocol) would be considered for efficacy assessment

· The data generated is subjected to normality test with Shapiro- Wilk test. If normality test is passed, parametric test would be employed otherwise non parametric test is employed.

· For objective data, paired‘t’ test will be employed to assess before and after treatment differences within the groups and unpaired ‘t’ test will be employed for assessing the differences within the groups.

· For subjective data, Wilcoxon signed rank test will be employed to assess before and after treatment differences within the groups.

· Mann- Whitney U test will be employed for assessing the difference between the trial and control groups.

· For multiple comparisons of more than 2 sets within the same group – repeated period of ANOVA for parametric data and Friedman’s test for non-parametric data would be used.

· P valve ≤ 0.05 will be considered as statistically significant.

· IBM SPSS Statistics application for Windows, version 26 will be used for analysis.

· Clinical effect size would also be determined using design appropriate methods

   Investigations:

1)CBC WITH ESR (0th  ,5th  day )

2. swab culture (0th,5thday)

3. Ph of lochia (5 consecutively days post NVD)

   Withdrawal criteria:

1.     Signs of sepsis (temp>100.4 F, pulse rate>90bpm, subinvoluted and tender uterus , wbc count more  than 12000cumm)

2.     Purulent or Blood stained lochia

3.     Breast abscess, mastitis

 ADR Reporting:

Adverse drug reaction will be reported to Pharmacovigilance centre of AIIA,New Delhi

 Translational Value:

1. Reducing the burden of antibiotic resistance
2. Protecting the child and the mother from adverse effects of systemic antibiotics
3. Holistic management of sutika by ayurvedic regimen
4. Cost effectiveness

 Rescue medication: Patient will be withdrawn from trial group and will be given antibiotics and painkillers or resuturing if needed

Patient Compliance :   A patient information sheet will be provided to patient in printed format. Information regarding the purpose, treatment plan, benefits and possible risks will be explained to the patient individually. Patients will be admitted in the ward for 5 days.

Drug Compliance :  A drug compliance chart will be given to the enrolled patients.

Data Confidentiality : Data collected during the study will be stored securely and will be used for analysis.

The Researcher, guide and co-guides, IEC, AIIA, New Delhi and other regulatory bodies will have access to the records.

Provision for Continued Patient Care: The patient will be handed over to the primary consultant for other routine medications (if required)

Monitoring of Study: Study will be monitored by the IRB committee, scholar, guide and co-guides

 References:

1.     Kaur H, Kaur S, Mattu S, Nandrajog A. Burden of puerperal sepsis and its relation with maternal mortality. International Journal of Reproduction,Contraception,Obstetrics,Gynecology 2023;12:3103-8

2.    Thitipong S. Incidence of postpartum infections and outcomes associated with antibiotic prophylaxis after normal vaginal delivery 2019,58;233-43

3.Top of Form

Dutta D.C, Textbook of obstetrics, Operative obstetrics,episiotomy,10th      edition,New Delhi:Jaypee brothers medical publishers,2023;p.259

4.     Mohammed NA,Hanafy NM,effect of post episiotomy antibiotics on maternal infectious morbidity, JRAM,2022;3(1);31-37

5. Chenyang Ji,Geer Zhang,Siyuan Xu,Qingyi Xiang,Meishuang Huang,Meirong Zhaoet al**.**Antibiotic treatments to mothers during the perinatal period leaving hidden trouble on infants, European Journal of Pediatrics,2022;181(9):1-13

6.    Shastri A D,editor,(1st ed.), Sushrut Samhita ,poorvardha, chikitsasthan, Chapter 2, verse 10. Varanasi: Choukhamba Sanskrit Sansthana ,2019; p.19

7.    Shastri A D,editor,(1st ed.), Sushrut Samhita ,poorvardha, sharirsthan, Chapter 10, verse 18.Varanasi:Choukhamba Sanskrit Sansthana,2019; p.103

8.    Shastri HS,editor,(1st ed.),Commentary by Arundutta and Hemadri on Ashtanga Hridayam of Vagbhata, Sharirsthan,Chapter10,verse 100/101, Varanasi:Choukhamba Sanskrit Sansthana,2022;p.102.

9.    Shaarma H,Vridhajivaka,Kashyap samhita,revised by vatsya with Sanskrit introduction with vidyotini hindi commentary,khilsthana,chapter 11,sutikupakramaniya,12,Varanasi:Choukhamba Sanskrit Sansthana,2000;  p.211.

10.      Gholap SR, Nar NV. Validation of the effect of an Ayurvedic procedure, Dashmoolkwath, and Dhoopan – fumigation with medicinal herbs during the first week of puerperium: An open clinical trial. Int J Ayurveda Med Sci. 2017;2(2):146-152.

11.       Mohite S.Determining efficacy of Combination of three ayurvedic formulations and dhoopana (medical fumigation  in prevention of infections post vaginal delivery with episiotomy), International Journal of Science and Research January 2013 ;4(1):2319-7064

 12.      Garthe, L. S., & Bhosale, R. R. Clinical Efficacy of Local Guggulu Dhoopana in Management of Episiotomy Wound. Ayurlog: National Journal of Research in Ayurved Science,2021; 9(03).

13.  Magar V and Gholap S , Evaluation of dhupan  karma in sutika paricharya. World journal of pharmacy and pharmaceautical sciences , 2017; 6(03): 607-621

14.      Bird SB, Dickson EW. Clinically significant changes in pain along the visual analogue scale,200;,38:639-643

15.      Rev Lat Am Enfermagem, Episiotomy healing assessment : REEDA scale reliability 2015;23(1);162-168

16.      Hitmer T. Physical and psychologic changes. In: Mattson S, Smith JE, editors. Core curriculum for maternal-newborn nursing. 4th ed. St. Louis, MO: Saunders Elsevier 2011; p. 301-314.