Indian Journal of Research in Homeopathy

RESEARCH PROTOCOL
Year
: 2019  |  Volume : 13  |  Issue : 3  |  Page : 177--183

A study protocol on comparative randomised controlled trial of Homoeopathy -vs- allopathy in acute otitis media and its recurrence in Children


Central Council for Research in Homoeopathy 
 Central Council for Research in Homoeopathy

Correspondence Address:
Central Council for Research in Homoeopathy
Director General, Central Council for Research in Homoeopathy, New Delhi

Abstract

Background: Acute otitis media (AOM) is one of the most common acute infections in children, and injudicious prescription of antibiotics may lead to increase of antibiotic-resistant cases. Homoeopathic treatment may provide a safer and more effective treatment. Objective: Earlier, a pilot study conducted by the Central Council for Research in Homoeopathy (CCRH) on eighty patients at a single centre showed non-inferiority results. This study shall be undertaken to substantiate the earlier findings. Methods: This will be an open-label, non-inferiority, randomised controlled (parallel arm) trial to be conducted on children in the age group of 2–12 years, suffering from AOM. The trial will include 240 children; each participant shall be randomly selected to receive either individualised homoeopathic medicine or symptomatic allopathic medicine. In case a child does not have ≥50% improvement with assigned treatment on day 3, he/she shall be given antibiotics. Children shall be treated/followed up for a period of 1 year to check recurrence, if any, in both the groups. The primary outcomes are changes in the Tympanic Membrane Examination Scale and Acute Otitis Media-Severity of Symptoms scale, time to improvement in pain through the Facial Pain Scale-Revised between the groups and recurrence (number of episodes, intensity and duration) of AOM between the groups at 1 year. Discussion: The study will consolidate the findings observed during a pilot study conducted by the CCRH at Jaipur, India. It is proposed to compare the role of individualised homoeopathy over allopathy in the treatment of AOM and to assess its role in controlling the recurrence.



How to cite this article:
Central Council for Research in Homoeopathy. A study protocol on comparative randomised controlled trial of Homoeopathy -vs- allopathy in acute otitis media and its recurrence in Children.Indian J Res Homoeopathy 2019;13:177-183


How to cite this URL:
Central Council for Research in Homoeopathy. A study protocol on comparative randomised controlled trial of Homoeopathy -vs- allopathy in acute otitis media and its recurrence in Children. Indian J Res Homoeopathy [serial online] 2019 [cited 2019 Dec 9 ];13:177-183
Available from: http://www.ijrh.org/text.asp?2019/13/3/177/268520


Full Text



 Introduction



Acute otitis media (AOM) is one of the most common disease in children. The usual symptomatic presentations characterising AOM are fever, irritability, otorrhoea, lethargy, vomiting, diarrhoea and hearing loss in some children.[1] The peak age-specific incidence is between six and fifteen months. Approximately 10% of children have an episode of AOM by three months of age and, approximately 50% to 85% of all children have experienced at least one AOM episode by three years of age.[2]

AOM is the general term embracing all inflammatory diseases of the middle ear, with particular involvement of the tympanic cavity.[3] The eustachian tube is the chief route by which infection reaches the middle ear. The most important cause is viral upper respiratory tract infection (URTI) followed by other opportunistic infections such as Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.[4]

Systematic reviews have demonstrated that the benefits of antibiotics must be weighed against the possible harms: for every 14 children treated with antibiotics one child experienced an adverse event (such as vomiting, diarrhoea or rash) that would not have occurred if antibiotics were withheld. Therefore clinical management should emphasise advice about adequate analgesia and the limited role for antibiotics.[2] i.e., preferring a watchful waiting in a majority of cases.[5],[6]

Homoeopathy is the most popular treatment among the complementary and alternative medicine therapies sought for OM.[7] Studies have been conducted which show the positive role of homoeopathic medicines over placebo, in treating AOM.[8],[9] Numerous clinical studies demonstrate that Homoeopathy accelerates early symptom relief in acute illnesses at much lower risk than conventional drug approaches. Evidence-based advantages for Homoeopathy include lower antibiotic fill rates during watchful waiting, fewer and less serious side effects, absence of drug–drug interactions and reduced parental sick leave from work.[10] In a prospective observational study carried out by one homoeopathic and four allopathy ear, nose and throat (ENT) practitioners, in treating acute paediatric OM, the homoeopathic single remedies were found to be beneficial in reducing the duration of suffering as well as the number of recurrences.[11] The existing research evidence on safety supports the pragmatic use of Homoeopathy in order to ' first do no harm' in the early symptom management of otherwise uncomplicated AOM.[10]

A pilot study conducted by Sinha et al.[12] compared individualised homoeopathic medicines in fifty millesimal (LM) potencies and symptomatic allopathic treatment including analgesics, antipyretics and anti-inflammatory drugs. Patients who did not improve were prescribed antibiotics at the 3rd day of treatment. Two different treatment therapies were compared which were found equally effective in AOM. However, symptomatic improvement was quicker in the Homoeopathy group, and there was a large difference in antibiotic requirements, favouring Homoeopathy.

In order to consolidate the findings observed in the pilot study, a multicentric study with larger sample size shall be undertaken to compare the treatment effects of Homoeopathy versus allopathy in AOM and further assess its role in controlling the recurrence.

Objectives

Primary – To compare the efficacy of homoeopathic treatment with allopathic treatment in AOM through changes in AOM-Severity of Symptoms (AOM-SOS) scale and Tympanic Membrane Examination scale, “time to improvement” in pain and “recurrence” of AOM in both treatment groupsSecondary – To evaluate the number of cases requiring antibiotic treatment, in both the groups, and to assess the quality of life (QOL) of children through Otitis Media-6 Health-related Quality of Life questionnaire.

 Methods



Study design

This is a national, multicentric, open-label, non-inferiority, randomised controlled (parallel arm) trial that shall include 240 children, suffering from AOM. The trial will be conducted according to the principles of the Declaration of Helsinki.[13] The Institutional Ethical Committee of the Central Council for Research in Homoeopathy (CCRH) approved the trial protocol (reference number 1-172/2011-12/CCRH/CR/CTRI 2102 dated 17 September 2013). The clinical trials registry number is CTRI/2014/12/005294 dated 15/12/2014. The schedule of enrolment, intervention and assessments following the Standard Protocol Items: Recommendation for Interventional Trials (SPIRIT) guidelines is presented in [Table 1].{Table 1}

Study setting

The study shall be conducted at the following ten centres under the CCRH: Central Research Institute (H), Noida (Uttar Pradesh); Central Research Institute (H), Kottayam (Kerala), now renamed as National Homoeopathy Research Institute for Mental Health; Regional Research Institutes (H), Jaipur (Rajasthan), Mumbai (Maharashtra), Guwahati (Assam), Imphal (Manipur), Gudivada (Andhra Pradesh), Drug Standardization Unit, Hyderabad (Andhra Pradesh) and Clinical Research Unit, Shillong (Meghalaya). ENT consultants shall be engaged to support the physical examination of ears and diagnosis and assess the patients for their symptom severity.

Eligibility criteria

Inclusion criteria are as follows:

Children aged 2–12 years who have earache of not more than 36 hoursFullness/heaviness in ear with or without signs of URTI and pain in ear with or without feverHistory of episode of AOM with proper record of diagnosis in the last 1 yearTympanic membrane bulging with loss of landmarks andWritten informed consent and assessment as appropriate.

Exclusion criteria are as follows:

History of convulsionsSubperiosteal abscess of mastoidGross deviated nasal septumAny discharge or history of discharge from earSuspected cases of gross adenoids (presenting with snoring and mouth breathing)OM with effusionPatients on antibiotics in the past 7 daysPatients on steroid treatmentPatients suffering from any systemic diseases.

Interventions

The children shall be allocated to either Homoeopathy or symptomatic Allopathy group in the ratio of 1:1.

Homoeopathic intervention – Group I

Homoeopathic medicines in centesimal potency (6C, 30C, 200C and 1M) shall be procured from Good Manufacturing Practices-compliant firms. These medicines shall be given following the Homoeopathy methodology of prescription. The selection of the individualised remedy (case analysis) will be carried out after the case history is taken by a homoeopath with more than 15 years of experience in classical Homoeopathy as described by Hahnemann.[14] The medicines shall be prescribed in centesimal potencies (6C/30C/200C/1M). Four pills of size 30 globules in the required potency will be administered. Indicated medicine will be repeated as per the need of each case i.e., 2–6 hourly or even oftener, depending on the intensity of symptoms.

Allopathy treatment intervention – Group II

Allopathic medicines for the trial shall be procured from any of the standard company, approved by the CCRH in consultation with the ENT specialist. Only symptomatic treatment shall be given by the ENT specialist to the patients for the first 72 hours (3rd day of treatment), such as analgesics for pain, antipyretics for fever, anti-inflammatory for inflammation and decongestants for congestion.

Follow-up common to both groups

During the episode of acute otitis media

Each patient will be followed up on the 3rd, 7th, 10th and 21st days in person during each episode of AOM. AOM-SOS scale and Tympanic Membrane Examination Scale (TMES) will be used for the diagnosis and assessment of patients with AOM by the ENT specialist/investigator. The study timeline is summarised in [Table 1].

On the 3rd day of follow-up, the ENT specialist will reassess the patients in both the groups on the AOM-SOS scale and TMES; if the symptomatic improvement is After the episode of acute otitis media-21st day

On the 21st day of the episode of AOM, after thorough case taking in the case-recording format for chronic case, the totality of symptoms shall be derived and repertorisation of the symptoms shall be done by using a suitable repertory (manually or using computer-based homoeopathic software). After repertorisation and consultation with the Materia medica, single homoeopathic medicine shall be selected as the prescription with justification for the respective patient. The remedy is prescribed in centesimal potency (6C/30C/200C/1M), with each dose comprising four pills of 30 size globules, repeated as per the need of the case. The OM-6 scale shall be used for the assessment of QOL in children suffering from AOM. This will be filled with chronic case taking, at the 6th month and at the 12th month.

As AOM is a disease of periodical nature and has seasonal variation, after the acute phase subsides, the constitutional/miasmatic/intercurrent medicine should be prescribed after detailed case taking on the 21st day of follow-up of the first episode of AOM. Follow-up of the patients shall be done every month for a period of 1 year to observe the recurrence. If any episode of AOM arises during the period of follow-up, it shall be treated and followed as done during the first episode and forms shall be filled and enclosed with the case record. Each case shall be followed up for 1 year from the period of enrolment.

In allopathic group, the ENT specialist will treat the patient during the follow-up period of 1 year as per the present symptoms/complaints of the patient, if any. If the patient requires some treatment other than AOM episode, then the ENT specialist will treat him/her accordingly. The investigator and ENT specialist will keep the record of all treatments given to patients during the 1–year follow-up period.

Outcome

Primary outcome parameters

Changes in the TMES and AOM-SOS scaleTime to improvement in pain through the FPS-R between the groupsRecurrence (no. of episodes, intensity and duration) of AOM between the groups at 1 year.

Secondary outcome parameters

Usage of antibiotics in both the groupsChanges in the QOL of patients as evident from the OM-6 HRQOL scale at the 21st day, 6 months and 12 months.

Sample size

The sample size calculation based on a previous study of AOM showed 99% improvement in the conventional group and 95% in the Homoeopathy group by the 21st day. Assuming the non-inferiority margin of Δ = 0.04, α = 0.05 and power of 90% (beta error of 0.10) necessary to show the significance 100 patients are needed per group. Considering the dropout of about 20%, 120 cases shall be to be enrolled in each group to obtain a total of 240 patients.

Recruitment

The patients shall be included in the study from the general outpatient department of the institute/unit on the basis of the presenting symptom(s)/sign(s) of AOM as per the inclusion criteria.

Randomisation

Randomisation shall be done in block size of two by using RALLOC software (Philip Ryan, 1997. “RALLOC: Stata module to design randomized controlled trials,” Statistical Software Components S319901, Boston College Department of Economics, revised 28 Jan 2018.). Centre-wise variable block randomisation will be done. Enrolment number of the patients shall be used for the purpose of randomisation. The ratio of allocation is 1:1. Initial randomisation shall be maintained for all follow-up visits.

Study duration

The study duration shall be of 2½ years including one year treatment period. This follow-up of 1 year is to observe the recurrence of acute episode, if any.

Statistical analysis

Data will be recorded on a pre-designed case-recording pro forma and will be managed on excel spreadsheet at each of the study centres. Finally, the data from all the centres will be combined together for analysis. Baseline characteristics of the study participants would be noted and compared in both the groups. The study outcome will be analysed according to parametric test for continuous data and non-parametric test for ordinal data after testing for normality. Baseline comparison would be considered for evaluating the randomisation effect. All the statistical results would be reported in 95% confidence interval with confidence level. For the outcomes of 'time to improvement' and 'recurrence', the approach of analysis would be based on 'time to an event data' (survival analysis). This would be done using Kaplan–Meier test. All analyses would be as per intention to treat. SPSS statistical software (IBM Statistical package for social sciences, version 20, India) would be used for data analysis.

 Discussion



AOM is a problem requiring frequent visits of children with their parents to their family physician/general physician and antibiotics are commonly prescribed for this condition.[15] Further evaluation of studies to determine whether antibiotic therapy influences the outcome of AOM has been difficult to interpret because of the high rate of spontaneous recovery in children with the disease. Overuse and misuse of antibiotics are key factors contributing to antibiotic resistance. The general public, doctors and hospitals all play a role in ensuring proper use of the medications and minimising the development of antibiotic resistance. Studies conducted earlier have shown the positive role of homoeopathic medicines in the treatment of AOM.[5],[8],[9]

The protocol has been developed as per the SPIRIT guidelines [16] and shall generate data that can be reported as per the CONSORT guidelines [17] and Reporting data on homoeopathic treatments (RedHot) supplement for reporting randomised trials of Homoeopathy (RedHot).[18] It has been identified that the best way to assess a causal relationship between cure and medicine is the randomised controlled trial. Medicines prescribed as per homoeopathic principles covering the entire symptomatology and individual aspects of each patient shall be helpful in improving the overall health and well-being of the patient. Further, the response of the effects of the remedies prescribed shall verify the results of the pilot study.

Further, this study involves administration of individualised homoeopathic medicine with the involvement of experienced homoeopathic doctors in treating patients suffering from AOM, using validated assessments, which will be amenable to the profession at large, thus covering all the domains of the model validity of homoeopathic trials.[19]

Contributors

Study concept, design and drafting of protocol: V.A. Siddiqui 1, Rupali Bhalerao 2, Varanasi Roja 3, Praveen Oberai 4

Drafting of manuscript: Varanasi Roja 3, Kiranmayee GR Rompicherla 5

Statistical planning: R M Pandey 6

Critical Review: Praveen Oberai 4

Funding/Support: Central Council for Research in Homoeopathy

1 Former Assistant Director (H)/Scientist-4, Central Research Institute (Homoeopathy), Noida

2 Research Associate, Central Council for Research in Homoeopathy, New Delhi

3 Research Officer (H)/Scientist-2, Central Council for Research in Homoeopathy

4 Research Officer (H)/Scientist-4, Central Council for Research in Homoeopathy

5 Research Officer (H)/Scientist-1, Central Council for Research in Homoeopathy

6 Head, Department of Biostatistics, All India Institute of Medical Sciences, New Delhi

Financial support and sponsorship

This study shall be financially supported by the Central Council for Research in Homoeopathy.

Conflicts of interest

None declared.

References

1Cripps AW, Kyd J. Bacterial Otitis Media: Current Vaccine Development Strategies. Immunol Cell Biol 2003;81:46-51.
2Venekamp RP, Sanders SL, Glasziou PP, Del Mar CB, Rovers MM. Antibiotics for acute otitis media in children. Cochrane Database of Systematic Reviews 2015. DOI: 10.1002/14651858.CD000219.pub4.
3Thomas JP, Berner R, Zahnert T, Dazert S. Acute otitis media – A structured approach. Dtsch Arztebl Int 2014;111:151-9.
4O'Neill P. Acute otitis media. BMJ 1999;319:833-5.
5Sakulchit T, Goldman RD. Antibiotic therapy for children with acute otitis media. Can Fam Physician 2017;63:685-7.
6Le Saux N, Robinson JL. Canadian Paediatric Society, Infectious Diseases and Immunization Committee. Management of acute otitis media in children six months of age and older. Paediatr Child Health 2016;21:39-50.
7Biswas AC, Joarder AH, Siddiquee BH. Prevalence of CSOM among rural school going children. Mymensingh Med J 2005;14:152-5.
8Jacobs J, Springer DA, Crothers D. Homeopathic treatment of acute otitis media in children: A preliminary randomized placebo-controlled trial. Pediatr Infect Dis J 2001;20:177-83.
9Frei H, Thurneysen A. Homeopathy in acute otitis media in children: Treatment effect or spontaneous resolution? Br Homeopath J 2001;90:180-2.
10Bell IR, Boyer NN. Homeopathic medications as clinical alternatives for symptomatic care of acute otitis media and upper respiratory infections in children. Glob Adv Health Med 2013;2:32-43.
11Friese KH, Kruse S, Lüdtke R, Moeller H. The homoeopathic treatment of otitis media in children – Comparisons with conventional therapy. Int J Clin Pharmacol Ther 1997;35:296-301.
12Sinha MN, Siddiqui VA, Nayak C, Singh V, Dixit R, Dewan D, et al. Randomized controlled pilot study to compare homeopathy and conventional therapy in acute otitis media. Homeopathy 2012;101:5-12.
13General Assembly of the World Medical Association. World medical association declaration of Helsinki: Ethical principles for medical research involving human subjects. J Am Coll Dent 2014;81:14-8.
14Hahnemann S. Organon of medicine, 6th edn. New Delhi: B. Jain Publishers (P) Ltd; 1979.
15Antibiotic management of acute otitis media. Paediatr Child Health 1998;3:265-70.
16Chan AW, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: Guidance for protocols of clinical trials. BMJ 2013;346:e7586.
17Schulz KF, Altman DG, Moher D. CONSORT Group. CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials. BMJ 2010;340:c332.
18Dean ME, Coulter MK, Fisher P, Jobst KA, Walach H. Reporting data on homeopathic treatments (RedHot): A supplement to CONSORT. J Altern Complement Med 2007;13:19-23.
19Mathie RT, Roniger H, Van Wassenhoven M, Frye J, Jacobs J, Oberbaum M, et al. Method for appraising model validity of randomised controlled trials of homeopathic treatment: Multi-rater concordance study. BMC Med Res Methodol 2012;12:49.