Comparative Study on Efficacy of Murvadya Churna with Lauha Bhasma and Navayas Churna in Pandu Roga (Iron Deficiency Anemia)

Pandu Roga is mainly the Rasapradoshaj Vyadhi which vitiates the Pitta. Whereas Shushruta described it as Raktapradoshaj Vyadhi. In Pandu Roga due to Alpa Rakta Twaka Vivarnata (discoloration of skin) occurs.So according to name Panduta is the main feature of Pandu Roga.Due to lack of dietary intake & improper absorption of iron are the causes of Iron deficiency Anemia. Aim: Efficacy of Murvadya Churna with Lauha Bhasma in the management of Pandu Roga (Iron Deficiency Anemia). Material and Methods: Study was contained 60 patients of Pandu were divided into two groups (each group contain 30). In Group A (Experimental group)Murvadya Churna with Lauha Bhasma 500 mg two times a day after meal with warm water for 30 days & In Group B 500 mg Navayas Lauha was administered two times a day after meal with honey. Assessment was recorded every 15 day (15 & 30 day) Result: Subjective and Objectives outcomes were assessed; both the groups were given equal effects on both the parameters subjective & objective. Conclusion: Murvadya churna with Lauha Bhasma was equally effective as Navayas Lauha. Study Protocol Davkare and Deshmukh; JPRI, 33(39B): 265-272, 2021; Article no.JPRI.68582 266


Background and Rationale
According to Ayurveda, body comprises of seven Dhatus, which are responsible for sustenance of the being. Amongst them the first Dhatu i.e., Rasa has given more importance. According to Charaka, Pandu Roga is a Rasapradoshaja Vyadhi which is a Pitta dominant Tridoshaja disease. [1] Whereas, Sushruta described it as Raktapradoshaja Vyadhi. [2] It is a disease in which Vivarnata of Twaka (discoloration of skin) is mainly Pandu (pallor/ yellowish-whitish) due to Alpa Rakta (reduced blood). [3] Other signs of Pandu Roga are Agnimandya (diminished appetite), Aruchi (tastelessness in food), Daurbalya (general debility), Bhrama (giddiness) etc. [4] The nearest correlation of Pandu Roga can be made with Iron deficiency Anemia, because of Panduta or pallor in the whole body.
Anemia means deficiency of Hemoglobin in the blood which can be caused by either too few RBCs or too little hemoglobin in the cells. [5] Anemia can be caused by innumerable factors, the most common being deficiency of essential elements for hemoglobin synthesis (Iron, Vit. B12 and folic acid), blood loss, repeated pregnancies in female of reproductive age, worm infestation, hemolysis due to known/ unknown causes and bone marrow conditions causing suppression of red cell synthesis. Anemia is a serious global public health problem & its prevalence is in young children & women. As per the National Family Health Survey, 53.2% of non-pregnant women and 50.4% of pregnant women of age 15-49 years were found to be anemic in 2016, whereas only 22.7% men were anemic in this age group. [6] Ayurvedic Herbo-mineral iron preparations being devoid of hazards need to be evaluated to know their efficacy in treatment of Pandu Roga. Since ancient times, different these iron preparations are empirically used for treatment of Pandu Roga. Murvadya Churna is one of such ayurvedic preparations. [7] On looking at the ingredients of Murvadya Churna, it works by effect on Srotasas (micro channels) and Agni (digestive fire mechanism). [8] In literature, there is no studies regarding usefulness of Murvadya Churna with Lauha Bhasma in treatment of Pandu Roga. Therefore, we were planned a study to analyze the effect of Murvadya Churna with Lauha Bhasma [9] in treatment of Pandu Roga (Iron Deficiency Anemia)

Trial plan
Block randomization criteria were fulfilled by participants and they were randomly selected for the experimental as well as controlled group with 1:1 ratio.

Type of Trial
This was the parallel group, single-blind, randomized, standard -controlled trial. The trial was including, a 30 days treatment period and 15 th day follow up period.
Allocation ratio -total 60 patients were selected for the study which will be divided into two equal groups. Group A is experimental group whereas Group B is standard controlled.

Interventions
Group A-Murvadya Churna with Lauha Bhasma 500mg two times a day with warm water after meal Group B -Navayas Churna 500 mg two times a day after meal with honey.

Randomization
Block randomization criteria were fulfilled by participants and they were randomly selected for the experimental as well as control group with 1:1 ratio. Researchers were access the treatment allocation for each eligible participant through a remote and web-based randomization system. Total 60 patients were selected for the study which were then be divided into two groups. Group A is experimental group whereas Group B is standard controlled.

Blinding
Treatment allocations was blinded to the participants, clinicians, research assistants, drug managers, statisticians, and other staff members, and we're not be revealed until the study was completed. The clinicians were assessed all the participants throughout the study period.. For each eligible patient, the clinician was applied for a randomized assignment by logging into the web-based randomization system, and prescription for "Murvadya Churna with Lauha Bhasma after meal with warm water two times a day" Then, accompanied with a research assistant, the patients were taken to the appointed drug managers at the Dattatraya Rasa Shala. During the trial periods, clinicians, research assistants, and drug managers are forbidden from discussing the assignment possibilities with the participants. All drugs are packaged in an identical manner. The blinding codes will be kept strictly confidential, and was not broken during the trial unless serious adverse events occur.

Criteria for Discontinuing or Modifying Allocated Interventions
From the study if any untoward incidence, features of drug sensitivity or any other disease or problem arises, Subject was withdrawn and free treatment will be offered to the subject till the difficulty subsides. We will measure quantity of Churna for the consumption of appropriate dose for assessment and to check drug adherence, during treatment the subject will be followed up.  Long-term effectiveness-Participants who will be weekly adequate relief responders for at least 30 days during the follow-up period will be considered longterm effectiveness responders.

Statistical Analysis
A level of 5% (two-sided) type I error will be considered as statistically significant. Analysis will be based on both intention-to-treat and perprotocol populations. Baseline characteristics, which also include predictive factors, will be presented for each group. From baseline to each time point, discrete variables will be described with frequencies and percentages, and continuous variables will be described with either mean and standard deviation for data with normal distribution or median and interquartile range for non-normally distributed data. For comparisons between experiment and control group at each time point, Wilcoxon test. Paired as well as Unpaired t test will be used to analyze the data having objective criteria. The McNamara's test will be used to analyze the data with subjective criteria. The analyses of predictive factors will be performed in two steps as follows: The first step is univariate analysis. The adequate relief followup (day 30) responder rates will be used as dependent variables, and predict factors, such as demographic and clinical characteristics, and key elements of Murvadya Churna with Lauha Bhasma, will be used as independent variables. A logistic regression analysis will be conducted. The selection criteria for the independent variable are defined as α = 0.1. The second step is multivariate analysis. Those predictive factors selected through the first step will be entered into two multiple regression models, taking the followup (day 45) adequate relief responder rates as the dependent variable.
Sensitivity analyses was planned. Firstly, the main and safety outcomes between all randomized patients and exposed patients were compared and then impact of missing data on primary outcome was evaluated.
Planned subgroup analyses will be carried out in relation to the primary outcome-adequate relief. The main analysis for each subgroup will be an unadjusted test of interaction in a logistic model.  Recruitment: By computerized simple random sampling method 60 patient will be recruited (30 in each group)  Implementation: Principal Investigator will enroll and allocate the patient. The intervention protocol was supervised by Principal Investigator by contacting the patients and follow up data of patients were stored in documentation with reason.
 Plan to promote participants retention and complete follow up: We will stay in touch with patient by taking contact no. and timely advise them for medication and follow up and data of follow up will be stored in documentation with reason.
 Data management: The data will be collected from patients by doing clinical evaluation. Data will be collected using planned questionnaire filled during interview of the patient. Data will be entered in master sheet and analysed by using suitable statistical technique and data coding will be done by principal investigator. Present in all sites 3

CONCLUSION
From the above study, it is concluded that, the interventional drug Murvadya Churna with Lauha Bhasma is 10% further more effective in Pandu Roga patient as compared to Navayas Churna with minimum side effects.

CONSENT
The written consent has been taken before starting the study from the patient. During the study, privacy should be maintained of each & every patient. Model consent form and other related documentation with all information has been given to participant.

ETHICAL APPROVAL
The study was approved by Institutional Ethics Committee Letter no. MGACHRC/IEC/AUG2020/93