| [Background]Postsurgicalgastroparesis syndrome of gastrointestinal tumors is a chronic condition of the stomach characterized by a delay in gastric emptying with no mechanical obstruction present, which is also a disease of gastric dynamic dysfunction. It is a very common condition, especially prevalent in postsurgical patients. It is reported that incidence rate is 0.6%-7%at home, and 5%-10% abroad, which shows rising tendency. The incidence of digestive system tumors has been increased year by year. The patients of digestive system tumors may live longer after surgery while long-drawn postoperative complications and physical discomforts decreased their quality of life, affecting the patients’confidence in postoperative recovery. Modern medicine treatment options for patients with PGS are limited.There were many reports of Traditional Chinese Medicine therapies on PGS, including both internal treatment and external therapies, with the efficiency rate 80-100%. It shows that the effect of the treatment varies between modern medicine treatment and TCM treatment. Yet few research report in Chinese on PGS provide evidence-based conclusions with high level, according to CNKI and Pubmed online database, which are only retrospective case series and simple case control studies, and also there has not been any research report on PGS with TCM for external use in Pubmed database up to now.Therefore, a high level of evidence-based clinical trial to demonstrate efficacy of TCM, will take full advantage of TCM on PGS and improve the present status of treatment on PGS. Based on our research on distribution of TCM syndromes on PGS in gastrointestinal cancer, this study is a double-blind, randomly assigned, placebo-controlled, multi-center study. Cold syndrome-based patients of PGS in gastrointestinal cancer with local syndrome differentiation were selected/enrolled, adopting" warming yang for dispelling cold and promoting qi to remove blood stasis" therapy, using "gastricparalysis decoction for external application", and evaluating therapeutic effects and prognosis. We hope the study will provide evidence of high level to benefit the patients in China and abroad.[Aims]1.To observe the therapeutic efficiency of’gastricparalysis decoction for external application’ for patients of PGS in gastrointestinal cancer.2. To evaluate the safety of’gastricparalysis decoction for external application’for the patients of PGS in gastrointestinal cancer.[Methods]A prospective, randomized, double-blinded, parallel-placebo multi-centers study was designed and carried out. The whole process, from the beginning to the end, was supervised by Beijing Qi Huang Medicine Clinical Research Center which was appointed by the sponsor Beijing Municipal Science and Technology Commission. After multiple arguments, the final version of research plan was set down. Before patient recruitment, we did the following preparations. The research was approved by ethics committees of all centers and registered at ISRCTN website. All researchers were trained and the technicians from drug manufacturing laboratory prepared the concentrated decoction which had been set double-blinded.Patients were recruited according to inclusion criteria and they would accept all the examinations at the beginning, including gastrointestinal endoscopy or upper endoscopy, abdominal computed tomography (CT) or erect abdominal plain radiography, blood, urine and stool routine tests, hepatic and renal function, electrocardiogram etc. Then they would get the drugs which were distributed sequentially in advance. Their recovery time of gastric dynamics would be recorded respectively on 1st,3rd,5th,7th,14th day, and also the gastricparalysis symptom scores, gastric drain volume, vomit volume and adverse drug reaction.Patients would complete the repeat testing as previously mentioned (as same as the base line/at the beginning of the study) when they finish the treatment. They also could get the true ’gastricparalysis decoction for external application" of 14 days for free if they wish for further treatment regardless of which group they had been in. The Evidence Based Medicine Center of BUCM would be in charge of locking the data. And the process of unblinding the drug types would be supervised by subject primarily responsible, the Evidence Based Medicine Center and staff from Beijing Qi Huang Medicine Clinical Research Center as third-party. After data analysis, we could draw conclusions of therapeutic efficiency and safety of’Gastroparesis external application decoction’for PGS patients via external application.[Results]1.The quality control of this clinical trial was rigorous throughout the whole process, and met the demand of our expectations. The content of quality control included:ethics committees permission; blind design; drug quality control; drug concentrated decoction preparation; trial registration; researcher training; patient recruitment; monthly quality supervision independently; data management and standard unblinding procedure. All the requirements above guaranteed the results true and precise.2. A total of 105 patients completed the protocol over the course of two years, among which 4 patients dropped out due to adverse reactions, and 2 patients had early termination due to adverse reactions, and 1 patient dropped out due to violating the protocol and 12 auto-quit. The course of treatment was 14 days. Baseline analysis:There were no statistical differences comparatively between the two groups("waifufang group" and placebo group) at age, drug allergy history, indwelling nasogastric tube, history of Chinese medicine treatment, postoperative gastric paralysis grading, classification of gastric paralysis symptom, tumor types, metastatic site, operation and incision type(P>0.05). There were no significant differences in clinical materials of two groups in demographics and examination at the time of enrollment (P>0.05). Therefore, two groups are comparable at baseline, which met randomized-controlled.3. The effective rate were respectively 68.33% and 68.9%(41/60 in true-drug group vs 25/60 in placebo group) according to FAS (full analysis set). There was statistically significant difference of effective rate between the two groups in FAS. The effective rate of the true-drug group was higher than the placebo group (P=0.003). Per-protocol population set (PPS) refers to cases which conformed to the protocol, with good compliance, following the instructions for taking the medication, completing the follow-up and CRFs. The effective rates were respectively 77.78% and 44.19%(35/45 in true-drug group vs 19/43 in placebo group) in PPS. There was statistically significant difference of effective rate between the two groups in PPS. The effective rate of the true-drug group was higher than the placebo group (P=0.001). There was still statistically significant difference of effectiveness rate between the two groups when dispelling the central effect (P=0.002)4. The secondary outcome of the study included time of effective treatment, the gastric paralysis symptoms before and after treatment, changes of the gastricparalysis symptom scores. It showed that there was statistically significant difference of time of effective treatment between the two groups both in FAS (P=0.017) and PPS (P=0.006). The recovery time for effective treatment of the trial group was shorter than the placebo group. Changes of volume of drainage of nasogastric tube did not show intergroup differences on 1st,3rd,5th,7th,14th day both in FAS and PPS. The gastric paralysis symptoms before and after treatment (eg:normal amount of intake, abdominal swelling after a meal) showed significant improvement compared with the placebo group. Changes of the gastricparalysis symptom scores showed statistically significant difference at different time spots both in FAS and PPS, while the two groups did not show differences on the gastricparalysis symptom scores.5.3 cases had adverse reaction in the true-drug group, and the occurrence rate is 5.66% (n=53).No adverse reaction was found in placebo group. No obvious difference of the incidence rate of skin allergy was found between two groups (P=0.244). The examinations after treatment, including blood test, urine test, stool test, hepatic and renal function, ECG and the level of serum potassium(K), natrium (Na) and chlorine(Cl) etc. showed no difference between the two groups(P>0.05).[Conclusion]1.The well designed and strictly supervised clinical trial was carried out, and this was a double-blinded, randomized, parallel-placebo, multi-sites study, which standards for a high level of evidence of evidence-based medicine. Therefore, the conclusions are reliable.2.The main outcome aim analysis showed that external application of Chinese medicine can improve the efficiency of clinical treatment of patients of PGS in gastrointestinal cancer under the guidance of TCM’cold and warm theory’. Gastricparalysis decoction showed a significant difference compared with the placebo group, which showed therapeutic advantage.3. The secondary outcome showed that the recovery time for effective treatment of the trial group was shorter than the placebo group with statistically significant difference. Changes of volume of drainage of nasogastric tube did not show intergroup differences on 1st,3rd,5th,7th, 14th day. The gastric paralysis symptoms before and after treatment (eg:normal amount of intake, abdominal swelling after a meal) showed significant improvement compared with the placebo group, while the following seven symptoms did not significantly improve between two groups:nausea, retching, vomiting, flatulency, loss of appetite, abdominal swelling and stomach or abdominal significantly extending. Changes of the gastricparalysis symptom scores showed statistically significant difference at different time spots, while the two groups did not show differences on the gastricparalysis symptom scores. Therefore,’gastricparalysis decoction for external application’group was not superior to placebo group on above-mentioned aspects.4. Traditional Chinese medicine external treatment may cause skin allergic reaction. In this study, the incidence rate was 5.66%(1 case had moderate dry decrustation itchy blisters,1 had Mild itching) when using the’gastricparalysis decoction for external application’. No risk of deterioration was found on the examinations during treatment, compared with the placebo group, which included abdominal computed tomography (CT) or erect abdominal plain radiography, blood, urine and stool routine tests, biochemical test(hepatic and renal function, the level of serum potassium(K), natrium (Na) and chlorine(C1)), electrocardiogram etc. |
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