Study of Effects of YisuiShengxueGranules on Thalassemia (thalessemia)
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|ClinicalTrials.gov Identifier: NCT01549080|
Recruitment Status : Completed
First Posted : March 8, 2012
Last Update Posted : March 8, 2012
|First Submitted Date||February 27, 2012|
|First Posted Date||March 8, 2012|
|Last Update Posted Date||March 8, 2012|
|Study Start Date||July 2011|
|Actual Primary Completion Date||October 2011 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures
||Clinical effects on heamoglobin changes [ Time Frame: 6 months ]
Changes from Baseline in heamoglobins at 3and 6 months
|Original Primary Outcome Measures||Same as current|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures
||Chinese Medicine syndrome improvment [ Time Frame: 6 months ]
changes from baseline in syndromes at 3 and 6 months
|Original Secondary Outcome Measures||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title||Study of Effects of YisuiShengxueGranules on Thalassemia|
|Official Title||A Double-blind, Placebo-controlled, Randomized, Parallel-group Study of the Safety and Effects of YisuiShengxueGranules on Thalassemia Presenting the Syndrome of Deficiency of Liver/Kidney-yin, and Asthenia of Essence/Blood.|
|Brief Summary||The primary objectives of this study are to evaluate whether Yisui Shengxue Granules therapy can increase the hemoglobin level in peripheral blood and alleviate the symptoms, and at the same time, evaluate its safety in the treatment of Thalassemia with the syndrome of deficiency of liver-yin and kidney-yin, and asthenia of essence and blood.|
3. INVESTIGATION PLAN 3.1 Study Design and Plan This study is a double-blind, placebo-controlled, randomized Parallel-group trial. Guang'anmen Hospital is the sponsor and has designed the clinical trial protocol. No.303 Hospital of Chinese People's Liberation Army (PLA) is the collaborator, where the most patients come from.
3.2 Random Method Using the randomized block design，stratifying by α-Thalassemia and β-Thalassemia, the patients will be allocated randomly 1:1 to Yisui Shengxue Granules group or placebo group.
Statistic Analysis System (SAS, SAS institute, Cary, NC, USA) was used to produce 001~120 random code, matching 120 subjects who divided randomly 1:1 into Yisui Shengxue Granules group and placebo group.
3.3 Blinding Design 3.3.1 Packaging of the study drug and placebo: all drugs including medical emergency envelops must be repackaged and reallocated according to regulations of standard double-blind clinical trial.
3.3.2．Blinding The encoded data will be kept in Guang'anmen Hospital, China Academy of Chinese Medical Sciences.
When all patients fulfill the procedures of the trial, the data will be entered into electronic Case Report Forms (eCRFs) and locked, and then the blind will be disclosed.
If unmasking is necessary because of a serious, unexpected and related adverse event or if a medical emergency occurs which requires knowledge of the exact therapy, the investigator may contact the principal investigator or censor to determine whether the medical emergency envelop will be broken. The date and reason of the code breaking must be documented and signed and this information must be sent to the sponsor and collaborator. The patient should be withdrawn from Study Medication but be followed up according to the protocol.
If twenty percent medical emergency envelops are broken or blinding method is betrayed, this trial will be fail.
3.4 Sample Size Estimation A total of 120 patients will be required (α-Thalassemia: 80, β-Thalassemia: 40 ), assuming a relative risk of sample loss (no more than 20%) in the whole trial-- an accrual period of 3 months treatment and a minimum 3 months follow up. The numbers of patients in both study drug group and placebo group are equal.
4.6 Removal of Patients from Study 4.6.1 Investigators make the decision of patients' withdrawal.
Investigators will decide to withdraw the patients if they have following conditions in the middle of the trial:
4.6.3 The case report forms of withdrawal patients, for whatever reason, must be kept. The last test results will be dealt with as the terminal results to enter the full analysis set. If the significant effects are showed up in less than 3 moths, the patients will be considered as significant effective cases though they complete the trial in advance.
4.7 Termination Criteria Trial termination means the study may be terminated at any time if the study represents a serious medical risk to the patients.
5.3 The Packaging Boxes and Preservation In a large packaging box, there will be three medium size packing boxes, containing 3 months dosage of Study Medication for one patient. The Study Medication can be either Yisui Shengxue Granules or placebo according to the random code, preserved by specially-assigned person and stored in dry environment at room temperature.
5.4 Drugs Assignment, Checking and Return Study Medication will be delivered to each clinical center according to the Study Medication code that randomly assigned to the clinical center, and be distributed to patients, who fulfill the inclusion criteria, in the order of drug code in 3 times. "Drug Used Report" should be filled in timely and kept by drug administrator.
Investigators should record the Study Medication quantity that patients received, took, and returned when they visit.
5.5 Drugs Blinding and Medical Emergency Envelope Study Medication blinding will be made by the corresponding department according to the randomization list. A medical emergency envelope, with detailed information of the medication, will be prepared for every randomization code and be kept in the principal investigator of each clinical center.
5.6 Precautions and Prohibited Drug Combination
6. OBSERVATIONS AND MEASUREMENTS 6.1 General Conditions (Before Entering the Trial)
6.2 Indexes for Safety Evaluation (Before and After the Trial)
(1) Temperature, blood pressure, respiratory rate and heart rate (2) Routine tests of blood, urine and stool (3) ECG (4) Liver function (ALT) (5) Kidney function (BUN, Cr) (6) Record any relevant adverse events 6.3 Indexes for Therapeutic Effects Evaluation 6.3.1 Major indexes
6.3.2 Secondary indexes
8. ADVERSE EVENTS 8.1 Adverse Event Record During the trial, if adverse events happen, the occurrence time, severity, duration, therapeutic measures and clinical outcomes must be recorded authentically in "DRUG ADVERSE EVENT FORM".
8.2 Severity of the Adverse Event
The severity of adverse events should be graded as follows:
Mild: Mild, tolerable discomfort, no need for special management, no influence to the trial and patient's rehabilitation.
Moderate: Moderate and intolerable discomfort, special management is necessary, having direct influence to patient's rehabilitation.
Severe: Severe discomfort, life-threatening, death or disability is possible and emergency intervention is necessary.
8.3 Relationship to Study Medication 8.3.1 Identification standards
8.4.2 Handling Procedure：Adverse reactions should be documented in CRF in detail including rechecking (when it is necessary), duration, prognosis and relief.
8.4.3 Serious Adverse Events Handling
8.4.4 Following up Adverse Events Unrelieved Any adverse events should be followed up until the adverse reactions relief or being stable.
|Study Design||Observational Model: Case Control
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Biospecimen||Retention: Samples With DNA
Peripheral blood and bone marrow cells
|Sampling Method||Probability Sample|
The type of severe β-Thalassemia：Hb <60g/L, microcytic hypochromic anemia; more than 10% target erythrocyte and erythrocyte fragments; increased number of reticulocyte; more erythroblast in peripheral blood; extremely proliferative in marrow; HbF>30%～90%.
The type of intermedia β-Thalassemia：Hb 60g/L～100g/L; the shape of mature erythrocyte is similar to severe type; more reticulocyte; erythroblast may be found; HbF>3.5%.
The type of intermedia α-Thalassemia： The patients have mild or moderate anemia (Hemoglobin in a few patients is less than 60g/L or more than 100g/L)，probably have hepatosplenomegaly, jaundice, and Mediterranean anemia features.
The Diagnosing Criteria for the Deficiency Syndrome of Liver-yin and Kidney-yin, and Asthenia of Essence and Blood in Chinese Medicine
|Intervention||Drug: Yisuishengxue Granule
Yisui Shengxue Granules，produced by pharmaceutical factory of Guang'anmen Hospital, China Academy of Chinese Medical Sciences, is made from the herbs of Shan Zhu Yu (Fructus Corni), He Shou Wu (Radix Polygoni Multiflori), Shu Di Huang (Radix Rehmanniae Preparata), Huang Qi (Radix Astragali) and etc.Yisui Shengxue Granules：12g/bag， Registration Number：20110602； Yisui Shengxue Granules replacer (placebo)：12g/bag，Registration Number：20110519；Treatment group：Yisui Shengxue Granules，1 bag, tid, po； Control group: Yisui Shengxue Granules replacer (placebo), 1 bag, tid, po; Intervention for 12 weeks. Follow-up 3 months later after stopping the drug intervention.
Other Name: Yisui Shengxue Granules replacer (placebo)：
|Publications *||Cheng YL, Zhang XH, Sun YW, Wang WJ, Huang J, Chu NL, Fang SP, Wu ZK. Genomewide DNA Methylation Responses in Patients with β-Thalassemia Treated with Yisui Shengxue Granules (). Chin J Integr Med. 2019 Jul;25(7):490-496. doi: 10.1007/s11655-018-2777-9. Epub 2018 May 3.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Original Actual Enrollment||Same as current|
|Actual Study Completion Date||January 2012|
|Actual Primary Completion Date||October 2011 (Final data collection date for primary outcome measure)|
|Ages||3 Years to 40 Years (Child, Adult)|
|Accepts Healthy Volunteers||Yes|
|Contacts||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries||Not Provided|
|Removed Location Countries|
|Other Study ID Numbers||2011001P02/June 3rd, 2011
2010CB530406 ( Other Grant/Funding Number: Ministry of science and technology "973" project )
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Wu Zhikui，Prof., Guang'anmen Hospital of China Academy of Chinese Medical Sciences|
|Study Sponsor||Guang'anmen Hospital of China Academy of Chinese Medical Sciences|
|PRS Account||Guang'anmen Hospital of China Academy of Chinese Medical Sciences|
|Verification Date||June 2011|