Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01549080 |
| Other study ID # |
2011001P02/June 3rd, 2011 |
| Secondary ID |
2010CB530406 |
| Status |
Completed |
| Phase |
N/A
|
| First received |
February 27, 2012 |
| Last updated |
March 7, 2012 |
| Start date |
July 2011 |
| Est. completion date |
January 2012 |
Study information
| Verified date |
June 2011 |
| Source |
Guang'anmen Hospital of China Academy of Chinese Medical Sciences |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
China: State Administration of Traditional Chinese Medicine of the People's Republic of China |
| Study type |
Observational
|
Clinical Trial 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.
Description:
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:
1. Upper respiratory tract infection with temperature higher than 38.5℃. This condition
will lead to hemolysis aggravation and hemoglobin level decreasing, affecting the
evaluation of therapeutic effects. The patients will be regarded as invalid cases once
they withdraw from the trial and accept other therapy.
2. Anemia complications or physiological changes make the patients being unsuitable to
continue in this clinical study.
3. Patients, with poor compliance, take the Study Medication less than 80% or more than
120%.
4. Unblinding cases and unmasking cases because of medical emergency.
5. Taking prohibited drugs.
6. Refusing to take any Study Medication. 4.6.2 Patients make the decision of their
withdrawal. In accordance with the World Medical Association Declaration of Helsinki
(1996 version), as amended from time to time, all patients have the right to withdraw
from the study at any time and for any reason, without prejudice to his or her future
medical care by the physician or institution, and is not obliged to give his or her
reasons for doing so. Without compromising the right of patients to withdraw from the
trial, every effort will be made to understand and accommodate their concerns and avoid
withdrawal wherever possible. If patients do not fulfill the therapy, tests, or
follow-up for any reason, the patients will be dealt with as removal from the study.
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.
1. Serious safety risk.
2. Gross error in the clinical trial protocol or major deviation appears during trial
execution.
3. Sponsor's request (reasons of finance, administration, etc.)
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
1. In this Trial, other drugs for β-Thalassemia are prohibited.
2. Patients, taking other drugs for other diseases, should be recorded in the item "the
table for being using other drugs for other diseases" in CRF.
6. OBSERVATIONS AND MEASUREMENTS 6.1 General Conditions (Before Entering the Trial)
1. Record age, gender, body weight and height.
2. Record past medical history: course of disease, diagnosis by Western Medicine and
Chinese Medicine, type of Thalassemia, course of treatment, combined diseases and
concomitant medication.
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
1. Clinical effects: screening visit (visit 1), visit 2 (4 weeks later), visit 3 (8 weeks
later), visit 4 (12 weeks later, the end of the medication therapy), visit 5 (follow-up
3 months later after medication therapy).
2. Chinese Medicine syndrome improvment: screening visit (visit 1), visit 2 (4weeks
later), visit 3 (8 weeks later), visit 4 (12 weeks later, the end of the medication
therapy), visit 5 (follow-up 3 months later after medication therapy).
6.3.2 Secondary indexes
1. Blood tests: white blood cell, hemoglobin, red blood cell, reticulocyte percentage,
hemoglobin eletrophoresis, fetal Hb, HbA2, HbH, platelet. Screening visit (visit 1),
visit 2 (4weeks later), visit 3 (8 weeks later), visit 4 (12 weeks later, the end of
the medication therapy), visit 5 (follow-up 3 months later after medication therapy).
2. Hepatic oblique diameter and spleen horizontal diameter by ultrasound imaging test
(Before and after trial).
3. Improvement of individual symptom: Screening visit (visit 1), visit 2 (4weeks later),
visit 3 (8 weeks later), visit 4 (12 weeks later, the end of the medication therapy),
visit 5 (follow-up 3 months later after medication therapy).
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
1. Whether there is a reasonable relationship between the time of taking Study Medication
and the occurrence of the suspected adverse reactions.
2. Whether the suspected adverse reactions accord with the adverse reactions known to the
Study Medication.
3. Whether the suspected adverse reactions can be interpreted as the results of drugs
combination, patient's clinical condition, or other therapies.
4. Whether the suspected adverse reactions disappear or are relieved by reducing the Study
Medication dosage or stopping to take.
5. Whether the suspected adverse reactions occur again at the time of retaking the
suspected drugs? Adverse Reaction Identification Conclusions Items 1 2 3 4 5 Sure + + -
+ + Probable + + - + ？ Undetermined + + ± ± ？ Unlikely + - ± ± ？ Unconcerned - - + - -
Note：+ Yes, - No, ± uncertain, ？Information is not available 8.3.2 According to the
above table, the relationship between adverse reaction and Study Medication will be
classified into 5 kinds as following: 1-sure, 2-probable, 3-undetermined, 4-unlikely
5-unconcerned The incidence rate of adverse reactions =（the number of cases with
adverse reactions including kind 1, 2 and 3）/（the number of cases which need to be
identified whether adverse reactions happen） 8.4 Adverse Event Handling 8.4.1 Handling
principle：Any adverse events such as patients' complaints and laboratory abnormality
should be taken seriously and analyzed carefully. Measures for managing adverse
reactions should be taken at once to protect the patients.
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
1. During the Trial, any serious adverse events must be reported to the clinical center,
sponsor and medical ethics committee and recorded in "DRUG ADVERSE EVENT FORM". All
clinical centers, principal investigators and the contact person listed on the CFR
should be informed as well at same time. Besides, a serious adverse reaction must be
reported to the State Food and Drug Administration within 24 hours.
2. Measures：If a medical emergency happens to a patient, the corresponding medical
emergency envelop will be broken by the principal investigator of the clinical center
in the presence of two witnesses. Proper management for adverse reactions will be taken
and CRA should be informed the outcomes. Investigators should write down the
information including unblinding reason, date, management and outcomes in CRF and sign
their names.
8.4.4 Following up Adverse Events Unrelieved Any adverse events should be followed up until
the adverse reactions relief or being stable.
