Home     Profile     Vaginitis     WH-1 Capsule     Safety & Efficacy     Clinical Trials     Business Opportunity     Contact
WH-1 A Breakthrough in the Treatment of Vaginitis
(White discharge in women)
WH-1 is an Ayurvedic Herbal Formula Developed by
Dr. V.R. Bapat, Bangalore, India. For his profile click here
He has experience of treating with this formulation over
a period of 35 years in his clinical practice.

 
 Clinical Trials
THE JOURNAL OF RESEARCH AND EDUCATION IN INDIAN MEDICINE

An International Quarterl                                                                                                             

Volume XVIII: 2                                 e Version                                             April - June, 2012

ISSN 0970-7700                                                                                              Pages 93-100

J. Res. Educ. Indian Med., April - June, 2012 Vol. XVIII (2): 93-10

EFFICACY AND SAFETY OF POLY HERBAL FORMULATION WH-1, FAS-3 KIT AND FLUCONAZOLE IN FEMALE PATIENTS WITH VAGINOSIS / VAGINITIS

 

KULKARNI CHANDA,1 DEB JARITA,2 MISHRA DEVESH,3 DIAS MARY,4
MHASKAR RITA,5 AND A.S. MOHAMMED

Division of Clinical Pharmacology, St. John’s Medical College, Bangalore - 560034 Karnataka (India)
1. Professor & Head Division of Clinical Pharmacology 2. Tutor Pharmacology 3. Lecturer Clinical Pharmacology 4. Assistant Professor, Microbiology 5. Professor, Obstetrics & Gynaecology 6. Assistant Professor, Community Health)

 

 

Abstract: Context: Vaginosis/vaginitis is one of the commonest symptoms in gynaecological outpatient setting and involves multiple causative organisms – bacteria, fungi and protozoa. The available treatment options produce a variety of adverse effects and do not decrease recurrence.
Aims: The purpose of this study was to examine if poly herbal formulation WH-1 has better efficacy and safety profile compared to the modern medication available for treatment of vaginosis/vaginitis.
Methods and Material: The present open labelled, randomized trial in adult women, with diagnosis of vaginosis/vaginitis, involved study patients in two groups who received either – WH-1 or standard treatment [FAS-3 kit or Fluconazole], based on microbiological evaluation. Efficacy outcome measures were assessed subjectively, clinically and microbiologically, while safety was assessed subjectively and using biochemical investigations. The data was analysed using unpaired‘t’ test, X2 test, and‘t’ test as appropriate.
Results: Between the groups comparison for demographic profile and chronicity of infection did not show significant difference. The clinical and microbiological improvement was comparable in two groups. The microbiological improvement in patients from both WH-1 and FAS-3 kit treated groups was similar while the adverse effects were significantly lower in patients treated with WH-1 [P < 0.05]. Conclusions: The efficacy outcome measures with poly herbal preparation WH-1 was found to be similar compared to standard treatment with lesser adverse effects. WH-1 may therefore be considered as a safer and alternative treatment option in subjects with vaginosis/vaginitis. However, studies involving long term treatment and follow up in larger number of patients are necessary to confirm the findings.
Keywords: WH-1, FAS-3 kit, Fluconazole, vaginosis, vaginitis, clinical evaluation, medicinal plants, Poly herbal formulations, Woodfordia floribunda, Cyperus scariosus, Bombax malabaricum, Symplocos racemosus and Caesalpinia bonduc.

Introduction

Vaginosis/vaginitis is one of the most common reasons for a female patient to consult a physician in a primary care setting. The infection often becomes chronic with difficulty in its eradication. The three most common types of acute vaginitis are Bacterial Vaginosis (BV) Vaginal Candidiasis (VC) and Trichomonal Vaginitis (TMV). It is reported that BV is the most common cause of vaginitis in reproductive age group accounting for 50% of cases with nearly 75% of all adult women having had at least one genital Candida infection in their lifetime.1
The standard treatment includes systemic/ topical antifungal, anti-protozoal and antibacterial agents, which decrease infection temporarily and often disrupt the normal vaginal flora which may lead to recurrent infection.
A preliminary single arm trial with WH-1 in the form of soft gelatine capsule containing -Woodfordia floribunda (Dhataki flower), Cyperus scariosus (Musta root), Bombax malabaricum (Mocharas gum), Symplocos racemosus (Lodhra) root  and Caesalpinia bonduc (Lata Karanja seed) is reported to be useful in BV, VC as well as TMV2 due to its antifungal, antimicrobial, antiseptic, astringent and demulcent properties.3 Therefore, the present study was designed to compare safety, efficacy and spectrum of activity of WH-1 with that of FAS-3 Kit and Fluconazole, in patients with vaginosis/vaginitis.

Materials and Methods

Study procedure, patient selection and randomization: The study was carried out by the Division of Clinical Pharmacology, in collaboration with the departments of Gynaecology and Microbiology after obtaining approval from Institutional Ethical Review Board and ICH-GCP- 2008 Seoul amendment and ICMR-2006 Guidelines were followed during the study procedure. The study was registered in Clinical Trial Registry of India [CTRI-020911479-0607200997748].
This was a randomized, open-labelled, comparative safety and efficacy study in subjects with vaginosis / vaginitis. Married women between 18 to 60 yrs of age, diagnosed to have vaginitis on the basis of symptoms, clinical and microbiological examination, were enrolled after obtaining written and informed consent from them as well as from their spouses. Pregnant and  lactating women, with clinical and biochemical evidence of major systemic disorder, women with multiple partners with history of alcohol, drug dependence, participation in any other study within  six weeks preceding day one of the present study, were excluded.
 An especially assigned case record form (CRF) was used to enter characteristic demographic data, and clinical symptoms of both acute [< 2 months duration] and chronic [> 2 months duration] vaginosis/vaginitis. The microbiological assessment was carried out to determine type of infection and subjects with confirmed diagnosis of vaginitis/vaginosis were then randomized manually to receive test or standard treatment.

Objectives

The primary objective was to examine the efficacy and safety profile of poly herbal test formulation WH-1 and compare the same with FAS-3 kit or Fluconazole. The spectrum of activity of study drugs against various organisms causing vaginitis/vaginosis was also evaluated.

Medication intervention

The study products WH-1, poly herbal preparation 650 mg capsule each and standard drug - FAS-3 kit or Fluconazole, were administered to two separate groups. The female study subjects along with respective partners also received study medications as a standard protocol. Group – A, received test drug WH-1, one capsule three times a day with water after food for a period of 10 days [composition Table 1].
Subjects under standard treatment Group –B, received contents of FAS-3 Kit [1 tablet Fluconazole, 150 mg, after breakfast; one tablet of Azithromycin 1 gm, one hour before lunch; and 2 tablets of Secnidazole 1 gm each after dinner] as a single dose. Subjects who were positive for Candida infection were randomized to receive Fluconazole 150 mg, stat or WH-1 as mentioned above. There was one follow-up on day fourteen.

Table 1 Components of White Haul Capsule [WH-1], with extracts of ingredient with quantity of each and Pharmacological properties as reported by FRLHT Plants of Ayurveda. (Weight of each capsule = 650 mg)

 

 

SN

Botanical Name

Ayurveda Name

Active Ingredient

Action and Uses

1

Woodfordia floribunda Flower

Dhataki

20 mg

Stimulant, Astringent, Tonic, used in Leucorrhoea and Menorrhagia

2

Cyperus scariosus root

Mustafa

40 mg

Carminative, Anti-bacterial, Antifungal

3

Bombax malabaricum gum

Mocharas

22.5 mg

Used in Dysentery, Leucorrhoea, Menorrhagia

4

Symplocos racemosus root

Lodhra

100 mg

Astringent, used in wound healing

5

Caesalpinia bonduc
seed

Latakaranja

50 mg

Antiseptic, Anti-parasitic, used in skin diseases

6

Ghee Clarified cow’s butter

Go ghrita

q.

Medium for formulation

 

Instructions to subjects

The study subjects and their partners were instructed not to take any other medication during the trial period. Compliance to study
medications and adverse reactions were monitored by counting the number of unused medications at each clinic visit and on the day of final follow up visit and recording through a calendar provided to each patient.

Assessment of safety and efficacy outcomes

The following subjective and microbiological assessments were carried out and compared on two occasions - prior to and after the treatment period to evaluate treatment outcomes.

1. Assessment of efficacy

a.  Subjective assessment for improvement in severity of symptoms viz. - itching, discharge, dysuria and dyspareunia was scored –Mild = 1, Moderate = 2 or Severe = 3.

b. Clinical assessment was by gynaecological examination for presence or absence of infection and was graded as - cured, improved, not improved or aggravated.

c. Microbiological assessment was carried out by collecting two vaginal swabs from each subject at the first visit and on day 14 after the treatment period and processed for –

(i) pH of vaginal smear using pH paper

(ii) Whiff test using 10% KOH and amine odour production. A strong fishy odour was considered suggestive of Bacterial Vaginosis [BV] 4

(iii) Vaginal smears, were subjected to Gram staining and graded based on Nugent score5, 6 for the diagnosis BV (iv) the wet mount preparation examined for presence of yeast cells, clue cells and actively mobile trophozoites as Trichomonas vaginalis [TMV]4

(iv) The wet mount preparation examined for presence of yeast cells, clue cells and actively mobile trophozoites as Trichomonas vaginalis [TMV] 4

 (v) Smear for diagnosis of candidiasis when showed presence of numerous yeast cells and pus cells4 

(vi) Presence of - bacteria, candida, trichomonals and numerous pus cells in a smear was grouped under mixed infection

(vii) lastly samples which did not fit into -Bacterial vaginosis, Candidiasis, Trichomoniasis; but had numerous pus cells with normal vaginal flora; or have altered vaginal flora showing abnormal Gram positive bacilli not resembling lactobacilli, or Gram negative bacilli not resembling Gardnella/Prevotella morphotype were categorised as nonspecific vaginitis. Smears with presence of Polymorphonuclears (PMNs) was graded in a semi quantitative manner as – none and +, ++, +++ representing - mild, moderate, and severe infection respectively.6
The follow up swabs collected from each of the subjects at clinic visit were processed similarly and microbiological improvement was considered as positive for –

(i) Bacterial vaginosis: when Nugent score dropped from > 6 before the treatment to < 3 after treatment

(ii) Vaginal candidiasis: with reduction in yeast cells and PMNs on Gram staining

(iii) Trichomoniasis: with absence of motile trophozoites in wet mount and

 (iv)Non-specific vaginitis: when reduction noticed in PMNs from +++ to ++ or +; from ++ to + or none, with return of lactobacilli as normal vaginal flora.

2. Assessment of Safety

Safety of treatment medications was by eliciting information subjectively through non-leading questions and biochemical investigations, carried out for female subjects entering the study and respective partners who received WH-1.
The adverse effects were graded as –Mild = 1, Moderate = 2 or Severe = 3 and were recorded from the calendar provided and categorised based on the system affected.
The Biochemical parameters were estimated on day zero and day 14 for those patients with respective partners who received WH-1 and included - random blood sugar (RBS), Kidney Function Tests (KFT) and Liver Function Tests (LFT). The values were considered normal when they matched with standard laboratory values. Since the safety of standard medications is well established patients in this group were not subjected for biochemical investigations.

Statistical analysis

The values for age distribution and chronicity of vaginal infection were compared between test and standard treatment groups using unpaired‘t’ test. The statistical analysis for parameters of microbiological and clinical improvement was carried out using x2 test. The comparison of subjective improvement in symptoms between the groups, and safety parameters for biochemical as well as adverse reactions were carried out using’ test and x2 test respectively.

Results

A total 57 female subjects with confirmed diagnosis of vaginitis/vaginosis were enrolled in the study. There were 48 subjects positive for mixed infection/nonspecific vaginitis and nine positive for candida. All subjects met the inclusion/exclusion criteria, were randomized to group A and B and 41 subjects completed the study; seven were lost for follow up and were considered as dropouts. Subjects positive for candida were not included in the statistical analysis.
 Twenty one subjects received study drug WH-1 and twenty subjects received standard treatment
(Table 2).
Table 2 the Mean ± SD values for age and chronicity of vaginitis in trial subjects treated under two groups

 

Treatment Groups

Number of patients

Age: Mean ± SD

Chronicity P > 0.05

Group A: WH-1

21

30.90 ± 8.03

Acute =15 , Chronic = 06

Group B: FAS-3 Kit

30

30.25 ± 9.52

Acute =12 , Chronic = 08

 

The test and standard treatment groups were homogenous with respect to age and chronicity of infection [P > 0.05] (Table 3). The improvement between the groups with respect to microbiological and clinical parameters calculated using x2 test did not show a significant difference [P > 0.05].
The difference in mean post – treatment values for subjective improvement when compared between the test [1.65 ± 0.988] and standard [2.50 ± 1.539] groups using unpaired students ‘t’ test, showed marginally higher improvement in the group which received standard treatment [P = 0.044].
The comparison of biochemical parameters between the two groups, as a part of evaluation of safety profile using‘t’ test, did not show statistically significant difference [P > 0.05]. The adverse reaction was seen in 1/21 patients in the test drug group viz. drowsiness, as against 6/20in the standard treatment group who showed mild – gastritis=2, diarrhoea=2, nausea and vomiting=1, body ache and fatigue = 1. The occurrence of adverse drug reactions was significantly higher among subjects who received standard treatment compared to group treated with test drug [x2 test, p = 0.0396].

Table 3 Comparison of subjective improvement of symptoms of vaginitis / vaginosis in patients receiving WH-1

 

Subjective improvement

Group A

Group B

P value

Pre-treatment

2.75 ± 1.517

3.27 ± 1.383

> 0.315
Not Significant

Pre-treatment

1.10 ± 1.210

0.7 ± 0.0733

> 0.214
Not Significant

Post treatment
Between groups

1.65 ± 0.988

2.50 ± 1.539

< 0.044
Significant

 

 

There were nine subjects who were microbiologically positive for Candida and among these; eight completed the study with one dropout. Five subjects from this group received WH-1 and three Fluconazole. They were analyzed descriptively after the treatment period. According to Clinical / Microbiological assessment in WH- 1 group, three patients improved while two did not, whereas in the Fluconazole group all three patients showed improvement.

Discussion

Several studies have been carried out to examine the factors influencing, as well as treatment outcome of bacterial vaginosis in terms of efficacy and safety.7 National Health Examination Analytic and Reporting Guidelines, have been formulated to study the condition (2005).8 It is well established that vaginosis when left untreated increases the risk of pelvic inflammatory disease [PID] in turn leading to infertility, premature delivery, low birth weight, in addition to endometritis and cervical neoplasia as some of its long term complications. Data clearly suggests that bacterial vaginosis is an important predictor of adverse reproductive outcome and more complete dynamics connecting the socio demographic characteristics is anticipated to create targeted interventions.9
Although BV is a common condition with distressing symptoms a high proportion of women remain asymptomatic. Change in vaginal ecology resulting in overgrowth of Gardnerella vaginalis and anaerobes with replacement of normal vaginal flora [lactobacilli] seem to be primarily responsible for this condition with recurrence leading to adverse pregnancy outcomes.b10 However, Clinical Guidelines from a review based on pooled data of several studies to examine value of screening and treatment of BV to reduce adverse pregnancy outcomes among asymptomatic women at various levels of risk for preterm delivery has turned out inconclusive.a.11 In the present study since pregnancy was one of the exclusion criteria it is difficult to comment on safety as well as usefulness of WH-1 in pregnant women with vaginitis.

Though, modern treatment options for systemic administration are available for bacterial vaginosis these are reported to have adverse effects. Furthermore, they are known to disturb the normal vaginal flora causing recurrent infection. While, only limited number of studies has evaluated the efficacy of Complementary & Alternative Medicinal [CAM] therapies, a systematic review on these for vaginitis has revealed that women particularly those with chronic vaginal symptoms increasingly rejected modern antimicrobial therapies in favour of alternative traditional remedies (96%) that are available and these were usually educated health conscious women.12 few of the specific therapies tested included – lactobacilli recolonization by oral and vaginal administration, douching, boric acid, tea tree oil and garlic. While, review supports the benefits of these ingredients, it has also highlighted the adverse effects associated with each of them. Comparative studies with various douching formulations either have revealed increased prevalence of PID, risk of ectopic pregnancy, endometritis and salpingitis associated with this procedure or some are in vitro to draw conclusive evidence on efficacy.13 Routine douching has been shown to double the risk of acquiring vaginitis. Further, boric acid treatment is reported to produce vaginal excoriation and use of topical tea tree oil or garlic is known to cause allergic reaction while oral garlic is said to produce heartburn and bloating.14 A trial with povidon-iodine as vaginal suppository for BV has shown some promising results.15 In addition the recommendations of previous review include - improvement in the study design, acceptable diagnostic criteria and examining validated outcome measures. The test preparation, WH-1 in the present study did not have any significant adverse effects. In this context the present study meets few of these recommendations such as study design, well defined assessment criteria, and outcome measures with reliable results, hence may be considered superior to earlier studies.

A preliminary study carried out elsewhere, with WH-1, revealed both symptomatic and clinical improvement in subjects with vaginitis of varied aetiology but this was not a comparative study. Also, objective assessment using microbiological parameters and statistical analysis was lacking in the previous study.3

 The present study was designed to evaluate systematically the efficacy and safety of test drug WH-1, in comparison with standard treatment regimen FAS-3 kit, in women suffering from mixed / non-specific vaginitis using subjective as well as objective criteria. The study also included assessment of lactobacilli count which was not a part of the earlier studies. The important efficacy parameters such as microbiological as well as clinical examination showed that WH-1 is equipotent to standard therapy. It is reported that the combination of antibacterial, antifungal and antiprotozoal agents in the modern therapy alter the normal vaginal flora leading to super infection and /or increasing chances of recurrence of infection. Interestingly, the present test preparation WH-1 showed absence of such associated complications. This finding appears to be unique to WH-1 and may be attributed to multiple mechanisms of actions of the various components of this formulation which are reported to reduce irritation, inflammation and secretion with added antiseptic activity.3

In addition either maintenance or improvement in the lactobacilli count was seen with WH-1, in the present study. In contrast 2/20 patients on standard treatment had aggravation of symptoms and super infection with candida respectively while only 1/20, had aggravation with super infection. Study by Bluestein C (1991) suggests possibility of predicting the occurrence of antibiotic induced Candidal vaginitis, this was not considered since the number of patients was small.16 Although, a long term follow up was not a part of the present study protocol, some patients were contacted telephonically at one to two months after completion of treatment with WH-1 and these showed subjective improvement compared to those who received the standard allopathic treatment, as far as relapse/recurrence was concerned. It is interesting to note that although the duration of treatment was ten days with WH-1 as against single dose treatment with standard FAS-3 kit, all patients except one demonstrated good compliance. This difference may be attributed to the fact that vaginitis/ vaginosis produces disturbing symptoms hence the patients may not be averse to taking medication for longer duration.

Patients with candida infection also showed clinical and microbiological improvement with WH-1, but the number of patients was small and so a statistical comparison to standard Fluconazole therapy could not be performed.

To conclude, our study confirms the observations of the previous preliminary study reports.3 WH-1 was found to be equally efficacious as standard drugs of FAS-3 kit and Fluconazole in mixed infection, nonspecific vaginitis as well as vaginal candidiasis. The numbers of adverse drug reactions [ADRs] were higher in standard modern treatment group.

 A few of the positive findings of the present study with WH-1 were its global efficacy in the treatment of vaginitis/vaginosis caused by multiple pathogens, minor incidence of ADRs, a noticeable increment in lactobacilli count, and 100% medication compliance despite longer duration of treatment. In addition there was no biochemical evidence of ADRs in patients who received test drug. Therefore WH-1 may be considered to be an effective and safe option for treatment of vaginitis/vaginosis.

However, studies in larger number of patients with longer duration of treatment as well as follow up are necessary to confirm benefits of WH-1, in preventing recurrence of BV, and in the treatment of VC or TMV as a complication of underlying diabetes mellitus, STDs or AIDs.

Key Messages

1. The safety and efficacy outcome measures with poly herbal formulation WH-1 in treatment of vaginitis/vaginosis revealed comparable efficacy profile with lesser adverse effects compared to modern medication.
2. Results are suggestive of WH-1 as one of the safer and alternative options in the treatment of vaginosis/vaginitis.

Acknowledgement

The authors wish to gratefully acknowledge Dr. V. R. Bapat, for free supply of WH-1 capsules and for financial assistance to conduct this study and Dr. S.C. Savitri, District AYUSH Officer, Govt. of Karnataka for her scientific input.

References

1. http://www.webmd.com/a-to-z-guides/vaginalinfections accessed on March 10 2012

2.  Ayurvedic Pharmacopoeia of India (API),Reference Vol.I, pp.32 & 82, serial 22, Vol.II,pp.93, serial 43 & 53, Vol.III, pp.129 & 183, serial 59 & 81.

3. Bapat VR, Alfred L, Shobha Rani RH, Ksheerasagar PT, Hegde G and Lund SK: Preliminary clinical study of poly herbal formulation (WH-1) in the treatment of vaginitis.
Indian journal of Pharmacy Practice 2009; 2(1):69-74

4. Spiegel CA, Amsel R and Holmes KK: Diagnosis of Bacterial vaginosis by direct Gram stain of vaginal fluid. Journal of Clinical Microbiology 1983; 18(1):170-177

5. Nugent RP, Krohn MA: Hiller SL. Reliability of diagnosing Bacterial vaginosis is improved by a standardized method of Gram stain interpretation.Journal of Clinical Microbiology 1991; 29(2):297-301

6. Vertaelen H, Verhelst R et al.: Modified classification of Gram stained vaginal smear to predict spontaneous preterm birth; a prospective cohort study. American Journal of Obstetrics and Gynaecology 2007; 196:528-29 June

7. Pirotta MV, Garland SM: Genital candida speciesdetected in samples from women in Melbourne Australia before and after treatment with antibiotics. J Clin Microbial 2006; 44(9):3213-7

8. Centre for disease control and prevention (CDC), national centre for health statistics (NCHS), nationalhealth and nutrition examination analytic and  reporting guidelines Yattsville (MD):U.S.department of health and human services, centres for disease control and prevention 2005

9. Allsworth JE, Peipert JF: Prevalence of bacterial vaginosis: 2001-2004 National Health and Nutrition Examination Survey data. Obstet Gynaecol 2007; 109(1):114-20

10. F Keane, Ison C A, Noble H and Estcourt C: Bacterial vaginosis. Sex Transm Infect 006; 82(Suppl IV):iv16–iv18. doi: 10.1136/sti.023119 2006

11. Nygren P, Fu Rongwei, Freeman M, Bougatsos C, Klebanoff M and Guise J:Evidence on the Benefits and Harms of Screening and Treating Pregnant Women Who Are 100 Kulkarni et al.Asymptomatic for Bacterial Vaginosis :An Update Review for the U.S. Preventive Services Task Force.148, 3, 2008. Ann Intern Med 2008; 148: 220-233

12. Kessel KV, Assefi N, Marrazzo J and Eckert L: Common complementary & alternative therapies for Yeast vaginitis & Bacterial vaginosis; a systematic review. Obstetrical & Gynaecological Survey 2003; 58(5):351-358

13. Pavlova SI and Tao L: In Vitro inhibition of commercial douche products against vaginalmicroflora. Infect. Dis Obstet Gynecol 2000; 8:99-104

14. Trutnovysky G, Law C, Simpson JM and Mindel A: Use of complimentary therapies in a sexual health clinic setting. International journalof STD and AIDS 2001; 12:307-309

15. Wewalka G, Stary A, Bosse B et al.: Efficacy of povidine-iodine vaginal suppositories in the treatment of bacterial vaginosis. Dermatology 2002; 204 (Suppl.1) 79-85

16. Bluestein D., Rutledge C. and Lumsden L: Predicting the occurrence of antibiotic induce Candidal vaginitis (AICV) Fam. Pract. Res.J. Pubmed 1991; 11:319-326

Address for correspondence:

 Dr.(Mrs.) Chanda Kulkarni, MD; PhD; FSASMS; Professor & Head, Division of Clinical Pharmacology, St. John’s Medical College, Bangalore – 560 034 Karnataka (India).
Email: drchandakulkarni@gmail.com

 

 
Copyright © reserved for Dr. V.R. Bapat