Colla Corii Asini Treating Anemia in Pregnant Women With Thalassemia(Presenting the Syndrome of Blood Deficiency)

Study Overview
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Brief Summary
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480 pregnant patients diagnosed of silent or standard α-thalassemia, HbH disease, minor or intermediate β-thalassemia with mild anemia will be randomly assigned to treatment group and control group. Patients in the treatment group will be given 15 g of Colla corii asini powder form daily for 8 weeks and followed up to 42 days postpartum while the control group will be observed and followed up in the same period treated with placebo. Levels of hemoglobin(Hb), reticulocyte (RET), immaturity reticulocyte (IRF), indirect bilirubin(IBIL), total bilirubin(TBIL), lactic dehydrogenase(LDH) will be measured on three visits(baseline, week 4 and week 8). The curative effect of TCM Syndrome( week 8) and undesirable pregnancy outcomes(42 days after giving birth) will be observed.

Detailed Description
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Thalassemia is a type of hemolytic anemia disease caused by genetic defect of synthesis in one or more globin chains. Among all the single genetic disorders thalassemia has the highest incidence rate in the world and causes heavy burdens on public health system. In China, the southern provinces suffer from high incidence of thalassemia, which is particularly common in the population of Guangdong, Guangxi and Yunnan provinces. Epidemiological studies showed that in Guangdong alone about 17.83 % of the 14,332 pregnant women across 21 regions examined were diagnosed as carriers of thalassemia . Recent studies showed that compared with healthy controls, women with thalassemia are associated with a wide range of abnormality and adverse pregnancy outcomes including cardiovascular disease, thrombotic disease, spontaneous miscarriage, premature delivery, oligohydramnios, fetal growth restriction and low birth weight. Currently there is no consensus on treating anemia in pregnant thalassemia patients. Due to the absence of an safe and effective therapeutic measures， many thalassemia patients are prone to develop low level of Hb, which can severely impact the fetal growth and maternal health. In traditional Chinese medicine (TCM), Colla corii asini (CCA, E'jiao) is a gelatin-like traditional Chinese medicine refined from donkey hide and has been widely used in clinical antanemic therapy for more than 2000 years. In the last decade, many studies had addressed the effect of CCA on the anemia using modern pharmacological approaches. The results indicated that CCA contains collagen protein,glycogen and a variety of trace elements, a variety of amino acids, etc. the main components of CCA can promote hematopoiesis by a number of mechanisms which eventually increase the peripheral erythrocyte counts and Hb concentration. Therefore, the investigators proposed that the hematopoietic effects of CCA might also contribute to the treatment of thalassemia with insuffcient or abnormal Hb concentration. The study aims to evaluate the efficacy and safety of Colla corii asini (CCA ) in improve anemia during pregnancy among silent or standard α-thalassemia, HbH disease, minor or intermediate β-thalassemia. Four hundred and eighty pregnant patients who meet inclusion criteria will be randomly assigned to either the treatment group or control group. Patients in the treatment group will be given 15 g of CCA daily for 8 weeks and followed up to 42 days postpartum, while the control group were observed and followed up in the same period treated with placebo. Levels of hemoglobin (Hb),reticulocyte (RET), immaturity reticulocyte (IRF), indirect bilirubin (IBIL), total bilirubin (TBIL), lactic dehydrogenase (LDH) will be measured on three visits (baseline, week 4 and week 8). The curative effect of TCM Syndrome( week 8) and undesirable pregnancy outcomes(42 days after giving birth) will be observed.

Official Title
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A Multi-center Randomized, Double-blind, Placebo-controlled Study of Colla Corii Asini for the Treatment of Anemia in Pregnant Women With Thalassemia(Presenting the Syndrome of Blood Deficiency)

Conditions
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Thalassemia

Intervention / Treatment
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* Drug: Colla corii asini
* Drug: a Simulate Agent of Colla corii asini granule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women diagnosed as thalassemia carriers by genetic test with clinical presentation of silent or standard α-thalassemia, HbH disease, minor or intermediate β-thalassemia; Patients with mild anemia (70 g/L≤ Hb<100 g/L) prior to study enrollment; Singleton pregnancy ; Gestational age between 24-32 weeks; Patients having not received blood transfusion in the last 12 weeks; Written informed consent of the patient. Exclusion Criteria: Known history of allergy or reaction to any component of the investigational product; Allergic to two or more drugs; Patients with severe thalassemia; Anaemia not caused by thalassemia (e.g., iron deficiency, aplastic, megaloblastic or haemolytic anaemia) or bone marrow diseases, leukemia. Twin or multiple pregnancies; Placental Abnormality (e.g., placenta previa, multilobate placenta, placenta succenturiate, placenta cirumvallate) or polyhydramnios, oligohydramnios, fetal growth restriction, fetal anomaly; Patients having received hemopoieticfactors or treated by hematopoietic stem cell transplantation in the last 2 months; Hypersplenism or hypertensive disorder in pregnancy; Patients with any of the following abnormalities: immunodeficiency, primary diseases involving cardiovascular system, liver, kidney, gastrointestinal tract, endocrine system and hematological system; 1.5 times or more higher plasma creatinine level than high limit of normal state; 1.5 times or more higher AST or ALT than high limit of normal state; Patients with mental illness; Patients who suffer from drug or alcohol abuse; Patients who addicted to smoking and drinking; Participation in any clinical investigational drug study within the previous 3 months; Patients who are regarded as ineligible for this study by investigator.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>15g of Colla corii asini granule( produced by Dong-E E-Jiao Co., Ltd) ， taken once daily for 8 weeks | Drug: Colla corii asini<br>* 15 g Colla corii asini granule daily for 8 weeks<br>* Other names: donkey-hide gelatin;|
| Placebo Comparator: Control group<br>a Simulate Agent of Colla corii asini granule， similar in size, shape，color and taste to Colla corii asini granule, taken once daily for 8 weeks | Drug: a Simulate Agent of Colla corii asini granule<br>* 15 g a Simulate Agent of Colla corii asini granule daily for 8 weeks<br>* Other names: Placebo of Colla corii asini granule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin(Hb) | the change of hemoglobin(g/L) | baseline, week 4 and week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| reticulocyte (RET) | the change of reticulocyte (RET)count（×10^9/L） | baseline, week 4 and week 8 | 
| immature reticulocyte fraction（IRF） | the change of immature reticulocyte fraction(%) | baseline, week 4 and week 8 | 
| adverse event | undesirable pregnancy outcomes | tracked for 42 days after giving birth | 
| indirect bilirubin(IBIL) | the change of indirect bilirubin(IBIL)(μmol/L) | baseline, week 4 and week 8 | 
| total bilirubin(TBIL) | the change of total bilirubin(TBIL) (μmol/L) | baseline, week 4 and week 8 | 
| lactic dehydrogenase(LDH) | the change of lactic dehydrogenase(LDH)(U/L) | baseline, week 4 and week 8 | 
| anaemia cure rates | anaemia cure rates(%):The concentration of hemoglobin was higher than baseline > 5g/L;The improvement rate = improved cases/the total number of cases * 100% | week 8 | 
| The curative effect of TCM Syndrome | the change of the TCM syndrome scores of two groups before and after treatment（%） | week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thalassemia;, the Syndrome of Blood Deficiency, Anemia, Colla Corii Asini