NHR Jan-Mar 2019: Original Research: Short Communication: Efficacy of Uva ursi in urinary tract infection in adults: Single-blind, randomized, placebo-controlled, pilot trial

Efficacy of Uva ursi in urinary tract infection in adults: Single-blind, randomized, placebo-controlled, pilot trial


Himangsu Hait*1, Samir Kumar Bhattacharyya2, Arup Das3, Rupali Bhaduri4,

Veena P Bharti4, Anjan Roy5

  1. Professor and Head, Department of Practice of Medicine, The Calcutta Homoeopathic Medical College and Hospital, Govt. of West Bengal
  2. Former Director, National Institute of Homoeopathy, Govt. of India
  3. Homoeopathic Medical Officer, Choa Primary Health centre, Murshidabad, West Bengal
  4. Lecturers, Dept. of Practice of Medicine, The Calcutta Homoeopathic Medical College and Hospital, Govt. of West Bengal
  5. Lecturer Dept. of Surgery, The Calcutta Homoeopathic Medical College and Hospital, Govt. of West Bengal

*Correspondence: haitdrhimangsu@gmail.com


ABSTRACT:

Background: Urinary Tract Infection (UTI) is one of the most common causes of infective illness and it has a great impact on quality of life. The aim of this pilot study was to evaluate the probable role of a homoeopathic drug Uva ursi beyond placebo in UTI and to explore the feasibility issues of a larger trial.

Method: A single-blind, randomized, placebo-controlled, pilot trial was conducted on 50 patients suffering from UTI in The Calcutta Homoeopathic Medical College and Hospital, West Bengal between mid-2013 and mid-2014. Intervention used was Uva ursi or identical looking placebo in individualized dosage. Routine examination, microscopy and culture of mid-stream urine specimen and symptom severity measuring Numeric Rating Scales (NRS) were taken as the primary and secondary outcomes respectively, measured at baseline and after 14 days.

Results: No patient dropped out, all enrolled and randomized (n=50) patients entered into the final analysis. In comparison with the placebo group, significantly higher number of patients improved in the Uva ursi group, thereby reflecting significant treatment benefit over placebo (p < 0.001, Fisher’s exact test).

Conclusion: Ultra-diluted and potentized Uva ursi produced significantly better effect than placebo in treatment of UTI. Larger trials and independent replications with enhanced methodological rigor are warranted.

Keywords: Uva ursi; homeopathy; efficacy; urinary tract infection, placebo, randomized trial


INTRODUCTION 

UTI is defined as multiplication of organism in the urinary tract. It is usually associated with the presence of pus cell and more than 100,000 organism/ml mid stream sample of urine. Common causative organism is Escherichia coli, which is commonly transmitted as ascending infection from peri-urethral area to urinary bladder [1, 2]. The incidence of UTI is 50,000 per million per year and accounts for 1-2% of patients primary care.  Almost all the cases of acute UTI present with frequency and urgency of  micturition, scalding pain in urethra during micturition, supra pubic pain during and after voiding, urine has an unpleasant odor, microscopic and/or visible haematuria, moderate to high fever and other constitutional symptoms. The density of motile bacteria (more than 105/ml) and presence of dead neutrophils in urine is the diagnostic marker of the disease [3-5]. The prevalence of the disease is an estimated 50% of women report having a UTI at some point in their lives. 8.3 million Office visits and more than 1 million hospitalized, for an overall around cost > $ 1 billion [6].

The improvement or cure of the disease is assessed by clinical improvement and reduction in the number of bacterial growth. It is easy to measure and interpret in a primary care setting; it is accurate, reproducible and internationally standardized. It has a favourable cost benefit ratio. Screening of culture for bacterial growth will also improve the patients’ management, particularly through most accurate risk classification and guidance in choice of therapy [1, 2]. Different homoeopathic medicines are claimed to act well in acute UTI, Uva ursi is amongst one of those [7-12]. Hydroquinone derivatives, mainly Arbutin and Methyle arbutin are the active principles [11-14]. This study tested whether homoeopathic Uva ursi can produce any significant effect beyond placebo in treatment of UTI.

METHODS

Trial design: This prospective, single-blind, randomized, placebo-controlled, parallel arm trial was conducted in the out-patient clinic no. 12 of The Calcutta Homoeopathic Medical College and Hospital. The study protocol was submitted and approved by the Institutional Ethics Committee [IEC/14/13(6), dated 20.05.2013] and was submitted to The West Bengal University of Health Sciences prior to enrolment.

Participants: Inclusion criteria were the patients suffering from UTI (ICD 10 code N39.0), aged 18-65 years, of both sexes, and written consent to participate. Exclusion criteria were concurrent presence of other systemic or infectious disease, currently receiving homeopathic treatment, congenital anomalies, diabetics, pregnant women, lactating mothers, substance abuse and/or dependence, self-reported immune-compromised state.

Diagnosis of UTI was based on the following points:

  1. Abrupt onset of frequency of micturition.
  2. Scalding pain in urethra during micturition.
  3. Supra pubic pain in urethra, during and after voiding.
  4. Urine has an unpleasant odor.
  5. Microscopic or visible haematuria
  6. Presence of pus cells in urine.

Intervention: In the intervention arm, Uva ursi was given in individualized dosage followed by placebo; each dose consisted of 4 cane sugar globules no. 30 medicated with a single drop of Uva ursi in desired potency, preserved in 90% v/v ethanol. In the control arm, identical looking placebo (indistinguishable from verum by appearance, smell, and taste) were given; each dose consisted of 4 cane sugar globules no. 30 moistened with a single drop of rectified spirit. Verum/control was instructed to be taken orally on clean tongue with empty stomach. Patients were advised to take plenty of water, normal diet and rest. Duration of intervention was 14 days.

Outcomes: Routine examination, microscopy and culture of mid-stream urine specimen and symptom severity measuring Numeric Rating Scales (NRS) were taken as the primary and secondary outcomes respectively, measured at baseline and after 14 days. NRS ratings were interpreted as per International Association for the Study of Pain (IASP) [15] as follows: No pain: 0, Mild pain: 1-3, Moderate pain: 4-6, and Severe pain: 7-10.

Sample size: Absence of any controlled trial of similar design precluded calculation of effect size and sample size. Hence, keeping assumed medium effect size (w) of 0.3, α=0.05, β=0.80 and provision 0f 15% attrition rate, to detect a significant difference in number of responders between the two groups through goodness of fit 2×2 contingency tables of chi-square test, required sample size would have been 100, i.e. 50 in each arm. However, prior to initiating a adequately powered trial, we thought it would be justified to conduct a pilot trial on 50 patients prior to enrolment into the main trial and check the feasibility issues.

Randomization: Method of alternation was adopted; i.e. every alternate patient was randomized to either Uva ursi or placebo to maintain the 1:1 allocation ratio.

Blinding: It was a single-blind pilot trial; only the participants were blinded to the allocated codes.

Statistical methods: Proportion of events (responders) occurring in the two groups over 14 days was compared using Chi square or Fisher’s exact test and p values less than 0.05 for a two-tailed test was considered as statistically significant. Reporting adhered to CONSORT [16] guidelines for reporting trials.

RESULTS

Study flow: In this study, 76 patients were screened, 50 were enrolled and randomized into verum (n=25) and placebo (n=25). After 14 days, all the patients were protocol compliant, none dropped out and all entered into the final analysis.

 

Recruitment: Starting from July 2013 until June 2014, 50 patients were enrolled and followed-up in the study.

Baseline data: Baseline symptom severity and count of pus cell per ml MSU are presented in tables 1 and 2.

 

Table 1: Baseline scoring of symptom severity

Symptoms of UTI None

(0)

Mild

(1-3)

Moderate

(4-6)

Severe

(7-10)

Total patients
1.      Abrupt onset of frequency of micturition 0 12 23 15 50
2.      Scalding pain in urethra during micturition 0 9 27 14 50
3.      Supra pubic pain in urethra, during and after voiding 3 16 18 13 50
4.      Urine has an unpleasant odor 9 13 22 6 50

Table 2: Baseline count of pus cells per ml MSU

Findings Cell count 0 Cell count 1-5 Cell count

6-10

Cell count 11-15 Total patients
1.      Abrupt onset of frequency of micturition 7 29 13 1 50
2.      Scalding pain in urethra during micturition 0 7 22 21 50

Table 3: Changes in symptom severity in the verum group (n=25)

Symptoms of UTI None

(0)

Mild

(1-3)

Moderate

(4-6)

Severe

(7-10)

Total patients
1.      Abrupt onset of frequency of micturition 16 7 2 0 25
2.      Scalding pain in urethra during micturition 14 8 2 1 25
3.      Supra pubic pain in urethra, during and after voiding 19 6 0 0 25
4.      Urine has an unpleasant odor 18 5 2 0 25

Table 4: Changes in count of pus cells per ml MSU in the verum group (n=25)

Findings Cell count 0 Cell count 1-5 Cell count

6-10

Cell count 11-15 Total patients
1.      Abrupt onset of frequency of micturition 21 3 1 0 25
2.      Scalding pain in urethra during micturition 19 4 1 1 25

Table 5: Changes in symptom severity in the control group (n=25)

Symptoms of UTI None

(0)

Mild

(1-3)

Moderate

(4-6)

Severe

(7-10)

Total patients
1.      Abrupt onset of frequency of micturition 1 3 8 13 25
2.      Scalding pain in urethra during micturition 2 2 6 15 25
3.      Supra pubic pain in urethra, during and after voiding 1 5 12 8 25
4.      Urine has an unpleasant odor 2 4 9 10 25

Table 6: Changes in count of pus cells per ml MSU in the control group (n=25)

Findings Cell count 0 Cell count 1-5 Cell count

6-10

Cell count 11-15 Total patients
1.      Abrupt onset of frequency of micturition 7 4 13 1 25
2.      Scalding pain in urethra during micturition 0 7 12 6 25

Table 7: Comparison of changes in symptom severity between groups

Groups No improvement Mild improvement Moderate improvement Marked improvement
Uva ursi (n=25) 5 4 11 5
Placebo (n=25) 18 6 1 0

 

 

Numbers analyzed: Outcome data from 25 patients from each group were analyzed.

Outcomes and estimation: Changes in both the groups over 14 days of intervention are depicted in tables 3-6 and a comparison carried out between groups on the changes are reflected in table 7. Uva ursi reflected significant treatment benefit over placebo (p < 0.001, Fisher’s exact test).

DISCUSSION

In our study, Uva ursi produced significantly better effect than placebo in treatment of UTI. The study was first of its kind evaluating the efficacy of a specific medicine Uva ursi in a single-blind, randomized, parallel arm, placebo-controlled design. The choice of Uva ursi was empirical, based on common symptoms and theoretical grounds, and because of absence of ‘characteristic’ symptoms from proving. Being a pilot trial, the authors warrant very cautious interpretation of the study results. Being fully aware that recruitment could be challenging, we developed a systematic recruitment strategy that included referrals from colleagues from other outpatients. It took 12 months to enroll and complete follow-up of 50 patients; thus undertaking larger trials seemed to be reasonably feasible keeping in mind an inclusion/screening rate of 50/76 = 65.8% and a retention rate of 100%. Media presence could have further enhanced the recruitment into the trial and achieve adequate power. Formal sample size calculation for the trial was not possible on account of absence of any study of similar design. The trial was open; no blinding was used. Thus, patient selection bias, treatment assignment bias, patient evaluation bias, and data analysis bias might have affected the outcomes of the study. In future research, alternative strategies including classic (individualized) approaches or other medicines enlisted for the said purpose may be subjected to similar controlled trials to arrive at a definitive conclusion.

CONCLUSION

Ultra-diluted and potentized Uva ursi produced significantly better effect than placebo in treatment of UTI. Larger trials and independent replications with enhanced methodological rigor are warranted.

Conflict of interest statement: The authors declare that they have no competing interests. The pilot trial was carried out as the PhD thesis of the corresponding author HH under guidance of SKB. Rests of the authors are teaching faculty of the institute.

Funding: We received no funding for the study. Funding required for the project was borne by the authors themselves.

Authors’ contributions: HH and SKB conceived and designed the study. HH, AD, RB, VPB, and AR collected data. HH ran the statistical analyses and interpreted the data. AD and HH prepared the manuscript. All the authors reviewed and approved the final manuscript.

Acknowledgements: We thank Dr. Subhranil Saha, Independent Researcher for his valuable inputs to improve the manuscript. The authors are grateful to the institutional heads of both academic and hospital section for their cooperation. We thank the colleagues, staff, pharmacists, and the patients for their sincere participation and contribution in the study.

 

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Cite this article as: Hait H, Bhattacharyya SK, Das A, Bhaduri R, Bharti VP, Roy A. Efficacy of Uva ursi in urinary tract infection in adults: Single-blind, randomized, placebo-controlled, pilot trial. National Homoeo Recorder 2019;15(1):46-51.

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