Clinical trial NCT03374111: Colla Corii Asini Treating Anemia in Pregnant Women With Thalassemia(Presenting the Syndrome of Blood Deficiency)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Thalassemia
Keywords: Thalassemia;
the Syndrome of Blood Deficiency
Anemia
Colla Corii Asini
Lead sponsor: The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
Sponsor class: OTHER
First posted: 2017-12-15
Enrollment: 480
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hemoglobin(Hb)
timeFrame: baseline, week 4 and week 8
Secondary outcomes:
measure: reticulocyte (RET)
timeFrame: baseline, week 4 and week 8
measure: immature reticulocyte fraction（IRF）
timeFrame: baseline, week 4 and week 8
measure: adverse event
timeFrame: tracked for 42 days after giving birth
measure: indirect bilirubin(IBIL)
timeFrame: baseline, week 4 and week 8
measure: total bilirubin(TBIL)
timeFrame: baseline, week 4 and week 8
measure: lactic dehydrogenase(LDH)
timeFrame: baseline, week 4 and week 8
measure: anaemia cure rates
timeFrame: week 8
measure: The curative effect of TCM Syndrome
timeFrame: week 8
Other outcomes:
Locations:
city: Dongguan
country: China
facility: The third people's Hospital of Dongguan
state: Guangdong
city: Guangzhou
country: China
facility: Intranet of Guangzhou Women and Children's Medical Center
state: Guangdong
city: Guangzhou
country: China
facility: the first affiliated hospital of Guangzhou University of Chinese Medicine
state: Guangdong
city: Guangzhou
country: China
facility: Department of Gynaecology and Obstetrics,Nanfang Hospital, Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Jinan University
state: Guangdong
city: Guangzhou
country: China
facility: The Fifth Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Dongguan Guangji Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen maternity and child health care hospital
state: Guangdong
city: Liuzhou
country: China
facility: Liuzhou Municipal Matemal and Child Health Hospital
state: Guangxi
city: Nanning
country: China
facility: The Guangxi Zhuang Autonomous Region National Hospital
state: Guangxi
city: Nanning
country: China
facility: Ruikang Hospital of Guangxi University of Traditional Chinese Medicine
state: Guangxi
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi University of Chinese Medicine
state: Guangxi
Study officials:
affiliation: the first affiliated hospital of Guangzhou University of Chinese Medicine ， Guangzhou
name: Yanfang Li, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li Y, He H, Yang L, Li X, Li D, Luo S. Therapeutic effect of Colla corii asini on improving anemia and hemoglobin compositions in pregnant women with thalassemia. Int J Hematol. 2016 Nov;104(5):559-565. doi: 10.1007/s12185-016-2069-0. Epub 2016 Jul 25.
citation: Cheng YL, Zhang XH, Sun YW, Wang WJ, Fang SP, Wu ZK. Clinical Effect and Mechanism of Yisui Shengxue Granules in Thalassemia Patients with Mild, Moderate, or Severe Anemia. Evid Based Complement Alternat Med. 2016;2016:1713897. doi: 10.1155/2016/1713897. Epub 2016 Feb 2.