ThalassemiaPhase 4NCT03374111
Colla Corii Asini Treating Anemia in Pregnant Women With Thalassemia(Presenting the Syndrome of Blood Deficiency)
A Phase 4 study testing Colla corii asini and a Simulate Agent of Colla corii asini granule in people with Thalassemia, run by The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine at 12 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 50 years, women only
- Conditions the study is for
- Thalassemia
- What is being tested?
- Colla corii asini and a Simulate Agent of Colla corii asini granule
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 480 participants
- Where
- 12 sitesChina
- Study dates
- 1 Mar 2018to 30 Dec 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 16Show fewer
- 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.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
China12 sites, 12 recruiting
- Not yet recruiting
The third people's Hospital of Dongguan
Dongguan, Guangdong, 523326
Lifang Mo, 13669853882, 478974155@qq.com
- Recruiting
Intranet of Guangzhou Women and Children's Medical Center
Guangzhou, Guangdong, 510405
shaoying Wu, PhD, 18902268157, wushaoying@163.com
- Recruiting
the first affiliated hospital of Guangzhou University of Chinese Medicine
Guangzhou, Guangdong, 510405
Yanfang Li, PhD, +86-20-36598857, gzyanfangli@hotmail.com
Song-ping Luo, professor, 13005156625, songpingluo@hotmail.com
- Recruiting
Department of Gynaecology and Obstetrics,Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, 510515
Zhijian WANG
- Recruiting
The First Affiliated Hospital of Jinan University
Guangzhou, Guangdong, 510630
Rui-man Li
- Recruiting
The Fifth Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510700
Junzhao Qiu
- Not yet recruiting
Dongguan Guangji Hospital
Guangzhou, Guangdong, 523382
Caifang Wang, 15817696003
- Recruiting
Liuzhou Municipal Matemal and Child Health Hospital
Liuzhou, Guangxi, 545001
Yuanliu Wang
- Recruiting
The Guangxi Zhuang Autonomous Region National Hospital
Nanning, Guangxi, 530001
Ruo xue You
- Recruiting
Ruikang Hospital of Guangxi University of Traditional Chinese Medicine
Nanning, Guangxi, 530011
Xin QIN
- Not yet recruiting
The First Affiliated Hospital of Guangxi University of Chinese Medicine
Nanning, Guangxi, 530023
Yong-qin Zhang
- Not yet recruiting
Shenzhen maternity and child health care hospital
Shenzhen, Guangdong, 518033
Yan Ning
About this study
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)
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.
Read the 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.
- Conditions
- Thalassemia
- Being tested
- Colla corii asini, a Simulate Agent of Colla corii asini granule
- Keywords
- Thalassemia;, the Syndrome of Blood Deficiency, Anemia, Colla Corii Asini
- Medical subject headings
- Thalassemia, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Colla corii asiniDrug
Also called donkey-hide gelatin
15 g Colla corii asini granule daily for 8 weeks
a Simulate Agent of Colla corii asini granuleDrug
Also called Placebo of Colla corii asini granule
15 g a Simulate Agent of Colla corii asini granule daily for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | 15g of Colla corii asini granule( produced by Dong-E E-Jiao Co., Ltd) ， taken once daily for 8 weeks Receives: Drug: Colla corii asini |
| Control group | Placebo comparator | 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 Receives: Drug: a Simulate Agent of Colla corii asini granule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hemoglobin(Hb)
the change of hemoglobin(g/L)
Measured: baseline, week 4 and week 8
Secondary outcomes (8)
reticulocyte (RET)
the change of reticulocyte (RET)count（×10^9/L）
Measured: baseline, week 4 and week 8
immature reticulocyte fraction（IRF）
the change of immature reticulocyte fraction(%)
Measured: baseline, week 4 and week 8
adverse event
undesirable pregnancy outcomes
Measured: tracked for 42 days after giving birth
indirect bilirubin(IBIL)
the change of indirect bilirubin(IBIL)(μmol/L)
Measured: baseline, week 4 and week 8
total bilirubin(TBIL)
the change of total bilirubin(TBIL) (μmol/L)
Measured: baseline, week 4 and week 8
lactic dehydrogenase(LDH)
the change of lactic dehydrogenase(LDH)(U/L)
Measured: 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%
Measured: week 8
The curative effect of TCM Syndrome
the change of the TCM syndrome scores of two groups before and after treatment（%）
Measured: week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2017
- Study start1 Mar 2018
- Primary completion1 Oct 2019 (estimated)
- Study completion30 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ThalassemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel Assignment
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 480 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yanfang Li, The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
- Investigators
- Yanfang Li, PhD, Principal investigator, the first affiliated hospital of Guangzhou University of Chinese Medicine ， Guangzhou
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03374111
- Sponsor's protocol ID
- TH-2
- Status last verified
- Dec 2018
- First submitted
- 4 Dec 2017
- Last updated
- 27 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all collected IPD, all IPD that underlie results in a publication
Publications
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.
PubMed 27456464Cheng 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.
PubMed 26949404
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03374111
- Acronym / sponsor ID
- TH-2
- Conditions
- Thalassemia
- Keywords
- Thalassemia;, the Syndrome of Blood Deficiency, Anemia, Colla Corii Asini
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 480 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital, Guangzhou University of Traditional Chinese MedicineUniversity, hospital or other
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 1 Oct 2019 (estimated)
- Study completion
- 30 Dec 2019 (estimated)
- First posted
- 15 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Parallel Assignment
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Drug: Colla corii asini15g of Colla corii asini granule( produced by Dong-E E-Jiao Co., Ltd) ， taken once daily for 8 weeks |
| Control group | Placebo comparator | Drug: a Simulate Agent of Colla corii asini granulea 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 |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (16 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Colla corii asiniAlso: donkey-hide gelatin15 g Colla corii asini granule daily for 8 weeks | Drug | Experimental group |
| a Simulate Agent of Colla corii asini granuleAlso: Placebo of Colla corii asini granule15 g a Simulate Agent of Colla corii asini granule daily for 8 weeks | Drug | Control group |
Primary outcome
Hemoglobin(Hb)
Time frame: baseline, week 4 and week 8
the change of hemoglobin(g/L)
8 secondary outcomes
reticulocyte (RET)
Time frame: baseline, week 4 and week 8
immature reticulocyte fraction（IRF）
Time frame: baseline, week 4 and week 8
adverse event
Time frame: tracked for 42 days after giving birth
indirect bilirubin(IBIL)
Time frame: baseline, week 4 and week 8
total bilirubin(TBIL)
Time frame: baseline, week 4 and week 8
lactic dehydrogenase(LDH)
Time frame: baseline, week 4 and week 8
anaemia cure rates
Time frame: week 8
The curative effect of TCM Syndrome
Time frame: week 8
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2018.
- Background: PubMed 27456464Li 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.
- Background: PubMed 26949404Cheng 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.
- Individual participant dataSharing planned: Yes. all collected IPD, all IPD that underlie results in a publication
Related trials for Thalassemia
Active, not recruiting
Evaluation the Safety and Efficacy of KL003 Cell Injection in the Treatment of Transfusion-dependent β-thalassemia.
Transfusion-dependent Beta-Thalassemia
RecruitingObservational study
Growth and Development-related Outcomes in Children With Transfusion-dependent Beta-thalassemia After Gene Therapy
Transfusion-dependent Beta-Thalassemia, Gene Therapy
Not yet recruiting
Gene Therapy of Beta Thalassemia Using a Self-inactivating Lentiviral Vector
Beta-Thalassemia
RecruitingPhase 1/2
β-Thalassemia Treatment With KL003 Cell Injection
Transfusion-dependent Beta-Thalassemia
Active, not recruitingPhase 3
A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT)
Non-Transfusion-dependent Alpha-Thalassemia, Non-Transfusion-dependent Beta-Thalassemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yanfang Li, PhD principal investigator
the first affiliated hospital of Guangzhou University of Chinese Medicine ， Guangzhou
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Colla corii asini and a Simulate Agent of Colla corii asini granule in people with Thalassemia, run by The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine at 12 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Song-ping Luo, PhD (13005156625, songpingluo@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hemoglobin(Hb) (time frame: baseline, week 4 and week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03374111, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2018.