Randomized, Double - Blind, Multicenter Clinical Study Of Allergic Purpura And Immune Imbalance Mechanism

purpose: 1.To evaluate the effectiveness and security of random、double blind and multi-centric clinical study about the Zidan granule and placebo treating the anaphylactoid purpura. 2. To discuss the pathogenesis of changing of the MMP-9 and VCAM-1 in anaphylactoid purpura.Material and Method: 1. The random、double blind and multi-centric clinical study of the Zidan granule and placebo treating the anaphylactoid purpura. 1.1 Method We use the method of random、double blind、multi-centric clinical study. The random took the method of partitions randomly, Use the SAS statistical software and made the random number table according to the cases of allotment and the rate of random from the participating hospitals. Double blind was operated by technicians who work in the China academy of traditional Chinese medicine clinical evaluation center. They numbered the medicines and carried out the double blind study about the investigators( clinical doctors、data administrators and data analyst) and subjects. Control: Under the premise of the same of basic treatment, making the placebo as the control group to observe the Zidan granule treating the anaphylactoid purpura. Multi-centric clinical study: There are five hospitals to finish the study together, they are the Liaoning university hospital of traditional Chinese medicine、Children’s hospital in Dalian、Combine traditional Chinese and western medicine hospital in Shenyang、Bejing university of traditional Chinese medicine Dongzhimen hospital、Chinese medicine hospital in Hunan province. 1.2 The research approach Dividing the 246 patients into treatment group(including 124) and control group(including 122). Treatment group: basic treatment + purple Dan particles., the control group used the placebo with basic treatment. The basic treatment: vitaminC(100mg/time, tid op), rutin(20mg/time, tid, op), and choosing the glucocorticoid in necessity. To take the Zidan granule 10 g, tid, under 10 years; 20 g,tid, above 10 years. The dose of placebo is the same as Zidan granule. The course of treatment is 4 weeks. Take the renal damage as the outcome event and evaluation index, then follow-up visit in a year. 1.3 Evaluation index 1.3.1 General data To observe the background(1) demography files: age、height、weight(2) general clinical files: complications and taking pills 1.3.2 Effect of indicators(1) Primary therapeutic effect evaluation The situation of outcome event(Renal damage situation): to describe the rate of outcome event and recurrence rate of anaphylactoid purpura when the study had finished in the double groups, and to use the method of chi-square test to compare the difference of the treatment group and control group.(1) asymptomatic hematuria or asymptomatic proteinuria(2) hematuria and proteinuria(3) acute nephritis(4) nephrotic syndrome(5) rapidly progressive glomerulonephritis(6) chronic nephritis(2) Subordinate therapeutic effect evaluation subordinate therapeutic effect index: traditional Chinese medicine syndrome total score、the primary symptoms score of traditional Chinese medicine syndrome、the subordinate symptoms score of traditional Chinese medicine syndrome and each symptom score. The disease outcome、The doctor of traditionalChinese medicine symptom curative effect.(3) Relevant chemical inspection(1) the count of urine erythrocyte and proteinuria qualitative: doing the test every two week and recording it one time.(2) urineβ2-microglobulin: doing the test every two week and recording it one time. Urine which has microalbumin: doing the test every two weeks and recording it one time.(3) the anaphylectogen from plasma: doing the test just one time and recording the result one time.(4) follow-up of 12 months: during the early 3 months, we done the test of routine urine one time each one week and recorded the result one time, done the test the urineβ2-microglobulin and urine microalbumin one time every two week and recording it one time. At the last 9 months, we done the test of routine urine one time every two week and recording it one time, done the test the urineβ2-microglobulin and urine microalbumin one time every one month and recorded one time. 1.3.3 Security index(1) Vital signs: blood pressure、respiratory、heart rate、temperature( doing the test one time in the point of before taking the medicine and after taking the medicine).(2) The test of blood routine、urine routine and stool routine( doing the test in the point of before treatment and after treatment)(3) Electrocardiogram、liver function test( ALT、AST)、renal function test( BUN, Cr)( doing the test one time in the point of before taking the medicine and after taking the medicine).(4) Adverse event(Detailed records at any time)2. The change and clinical significance of MMP-9 and VCAM-1 from the patients who had anaphylactoid purpura during the acute period. 2.1 The objective of study: to choose the patients who saw a doctor from February to September, 2014 in the Liaoning university hospital of traditional Chinese medicine expert outpatient service. There were 60 patients who had the anaphylactoid purpura in the acute period and 30 healthy children come from a primary school. 2.2 Collecting the cases: we got the plasma from the patients in 1.8ml, and put them in the tube with citron acid sodium anticoagulation, then centrifuged the plasma about 20 minutes by 1000r/min, after that we got and number the serum, at last, put the refrigerator to test. 2.3 The method of test: Using the ELISA to test the MMP-9 and VCAM-1 from the 60 patients of plasma in the acute period and 30 healthy children’s plasma.Result: The study has 256 cases in random(treatment group has 128 cases, control group has 128 cases), none of them has rejected, 10 cases have lost. FAS has collected 256 cases(treatment group has 128 cases, control group has 128 cases), PPS has 246 cases(treatment group has 124 cases, control group has 122 cases), SS has 256 cases(treatment group has 128 cases, control group has 128 cases). 1. Base line: There are no statistical significance(P﹥0.05) and has comparability in demogracy characteristic、dignosis、medical history for treatment、allergic medical history and physical examination. There are no statistical significance(P﹥0.05) and has comparability in the total points of syndrome score、prime symptom score、subordinate symptom score、urineβ2-microglobulin、urine microalbumin、uric red blood cell and uric protein. 2. Primary therapeutic effect index The rate of the renal damage of outcome event: 8 cases(6.45%) had the renal damage events in the treatment group after study: hematuresis had 2 cases、proteinuria had 2 cases、asymptomatic hematuria or/and asymptomatic proteinuria had 6 cases. 19 cases(15.57%) had the renal damage event in the control group: hematuria or/and proteinuria had 5 cases, asymptomatic hematuria or/and asymptomatic proteinuria had 14 cases. As a result, the renal damage rate of the two groups had statistical significance through the method of chi-square test. 3. Subordinate therapeutic effect index(1) The total points of syndrome score: 14 days after the treatment and 21 days after the treatment had statistical significance in the different group through the Group T test, and the rest of others had no statistical significance about the total point of syndrome score.(2) Prime symptom score: 14 days after the treatment and 21 days after the treatment had statistical significance in the different group through the Group T test, and the rest of others had no statistical significance about prime symptom score(3) Subordinate symptom score: there was no statistical significance in the different group about the time point after the treatment about subordinate symptom score. Each single score of syndromes of traditional chinese medicine: Petechiae, ecchymoses part: starting from 14 days after the treatment, the change situation of relative to the baseline of two groups had statistically significant through the rank test. There are three time points which were after giving the medicine had statistically significant :14 days, 21 days and 28 days. The rest of time points had no statistically significant. Color, abdominal pain, hematochezia, joint swelling, joint pain, pharynx red, sore throat: The change situation of relative to the baseline which were from different time points after treatment had no statistically significant between twogroups. 4. Security There were 2 cases adverse events during the research, both of them were catching a cold. And the other cases had no adverse events. 5. The situation of drug combination Both of the treatment group and the control group had similar drug combination during the study. There were obvious statistical significance about the using rate of the glucocorticoid in the basic therapy, the using rate of control group of glucocorticoid was higher than the treatment group obviously. 6. The disease outcome and syndromes curative effect of Traditional Chinese Medicine comparison : There were no statistical significance about the criterion of the therapy effect and the syndrome of Traditional Chinese Medicine through the rank sum test after the study. 7. The VCAM-1 and MMP-9 of the plasma in the anaphy lactoid purpura group was higher than normal group(P<0.05) during the acute period and had statistical significance.Conclusion 1. The foundation of anaphylactoid purpura is the pathological evolution of heat、toxin and blood stasis.2. Zidan granule could reduce the rate of renal damage, it shows that taking the herbs in the early stage to treat the anaphylactoid purpura had important implication. 3.Taking the method of detoxification、cooling blood and dispersing blood stasis in the early stage to treat anaphylactoid purpura could improve the bleeding symptom rapidly. 4.Taking the method of detoxification、cooling blood and dispersing blood stasis in the early stage to treat anaphylactoid purpura could reduce the rate of using theglucocorticoid. 5.The VCAM-1 and MMP-9 of plasma from the patients who had the anaphylactoid purpura become higher obviously, it means that anaphylactoid purpura had important endothelial cell damage and extracellular matrix damage,From the perspective of cytokines allergic purpura immune mechanism of the disease are discussed. 6. Anaphylactoid purpura is a the injury of Yang-collateral, it caused by heat and toxin, blood stasis, its major mechanism is the cell immune function imbalance. Therefore anaphylactoid purpura is a cell immune imbalance situation causing by injury of Yang-collateral.