Effect of Ejiao Compound in the Treatment of Postpartum Anemia of Qi-blood Deficiency Syndrome

Effect of Ejiao Compound in the Treatment of Postpartum Anemia of Qi-blood Deficiency Syndrome: Study Protocol of a Randomized Controlled Trial

The prevalence of postpartum anemia is a great threat for maternal and infant health without timely and effective treatment. Oral iron therapy has been used for centuries as a treatment of anemia, however, it is noteworthy that treatment with oral iron might have a limited, and even a harmful role in some clinical scenarios. Ejiao compound is composed with donkey-hide glue, Ginseng, Codonopsis pilosula, prepared rhizome of rehmannia, and crab apple, which has been widely used in the treatment of various types of anemia in China for decades and might be a potentially effective therapy for postpartum anemia. Recently, studies involving animal subjects have helped shed light on its mechanism of action.

In this study, the investigators aimed to conduct a randomized controlled trial to assess the efficacy and safety of Ejiao compound comparing with oral iron in the treatment of mild postpartum anemia with or without iron deficiency.

Study Overview

• Status: Unknown
• Conditions: Postpartum Anemia
• Intervention / Treatment: Drug: Ejiao compound; Drug: Niferex

Detailed Description

1. Study type: This is a randomized, parallel controlled and single blind study. The sample ratio of the experimental group and the control group will be 1:1.
2. Study Setting and Recruitment: All participants experience vaginal delivery and are diagnosed with mild postpartum anemia. They will be recruited from the obstetric inpatient department in two hospitals: the first affiliated hospital of Guangzhou University of Traditional Chinese Medicine, and Maternal and Child Health Hospital of Panyu District in Guangzhou City. All assessments and interventions will occur at hospitals.
3. Randomization, blinded method, and allocation concealment: Patients meeting the criteria were randomized into experimental group or control group, according to a computer-generated list. The patients in experimental group will receive the treatment of Ejiao compound while the patients in control group will be treated by Polysaccharide iron complex. The study physicians will receive a sealed decoding envelope per treatment, they will not know the identity of the participants, will not handle the study products, will not know the assigned treatment, and will not share their own examination results. After receiving the evaluation by the study physicians and finishing the investigation form, the patient will take her own sealed decoding envelope and go to the pharmacy of the clinical trial center to receive her medication. The staff of the pharmacy of the clinical trial center is responsible for the distribution and return of experimental drugs to patients. All envelopes, sealed or unsealed, will be returned to the investigators at the end of the study. Patients would be required to return boxes whether they are used and unused at each visit and compliance will be assessed by counting the bottles and capsules.
4. Sample size calculation: It was reported that treatment with oral iron for anemia in postpartum women increase the Hb concentration by 49.3% by day 40. Combined with etiological treatment, Ejiao compound used to treat anemia in non pregnant population for three months, the Hb concentration increased by 66.9%. Basing on the results of literatures mentioned above, the investigators suppose that the difference of Hb concentration between patients only receiving the Ejiao compound for 4 weeks and patients only receiving oral iron for 4 weeks would be 25.0%. The α-value is set at 0.05 and the test power is 0.90. The final sample size should be 68 in each group. With an anticipated dropout rate of 20% during the follow-up, the initial sample size for each group should be 85, and 170 in total for two groups.
5. Statistical analysis: The statisticians will be blinded to the allocation of the participants. Statistics Package for Social Science (SPSS)19.0 statistical software packages will be used to analyze the data. The intention-to-treat population will include all randomized patients who receive the assigned treatment at least once, and who have an evaluation of outcomes. The measurement data will be analyzed by using t-test or the rank sum test, and the numeration data will be analyzed by using chi-square test or Fisher's exact test. P<0.05 indicates statistical significance.

• Study Type: Interventional
• Enrollment (Anticipated): 170
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510405
      • Recruiting
      • the First Affiliated Hospital, Guangzhou University of Chinese Medicine
      • Contact: Yanfang Li, PhD; Phone Number: +86 13928777126; Email: gzyanfangli@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women aged 18 years to 45 years with mild postpartum anemia (Hb <10 g/dl and ≥7 g/dl at 24-48 hours postpartum);
2. Absence of antepartum anemia, which is defined as Hb≥11.0 g/dL within 48 hours before delivery;
3. Singleton pregnancy;
4. Type of syndrome in Traditional Chinese Medicine is "Qi-blood deficiency".
5. Patients having not received blood transfusion or any forms of anti-anemia treatment in Western medicine or TCM in the last 12 weeks;
6. Informed consent obtained.

Exclusion Criteria:

1. Type of syndrome in TCM is NOT "Qi-blood deficiency";
2. Antepartum anemia;
3. Twin or multiple pregnancies;
4. A history of haematological disease (e.g. sickle cell anemia or thalassemias);
5. A history of undigestive disease (e.g. gastric ulcer, gastritis) or inflammatory bowel disease;
6. A history of cardiovascular diseases, renal or liver disease, asthma, thromboembolism, HIV infection, tuberculosis, cancer and seizures;
7. Patients having received blood transfusion or any forms of anti-anemia treatment in Western medicine or TCM in the last 12 weeks;
8. Alcohol or drug abuse;
9. Patients with mental illness or poor compliance to medical treatment;
10. Participation in another clinical trial within the previous three months;
11. No informed consent obtained.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ejiao compound; The participants in experimental group receive Ejiao compound (20ml, twice daily) orally for 4 weeks.	Drug: Ejiao compound; 20ml,twice daily, orally after breakfast Duration:4 weeks; Other Names: Chinese patent medicine
Active Comparator: Niferex; The participants in control group receive Polysaccharide Iron Complex(Niferex)(150mg per tablet, once daily) orally after breakfast over 4 weeks.	Drug: Niferex; one tablet,once daily, orally after breakfast Duration:4 weeks; Other Names: Polysaccharide Iron Complex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hemoglobin(Hb)	before and after treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum ferritin	before and after treatment
Life quality assessment: a Health Assessment Questionnaire(The Short Form-36 Health Survey, SF-36)	before and after treatment
Traditional Chinese Medicine symptom score:a self-made scale for Qi-blood Deficiency Syndrome	before and after treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse reactions or events: renal function	serum creatinine and urea nitrogen	before and after treatment
Adverse reactions or events: liver function	aspartate aminotransferase(AST), alanine aminotransferase (ALT)	before and after treatment

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
• Investigators: Study Chair: yanfang Li, PhD, the First Affiliated Hospital, Guangzhou University of Chinese Medicine

Publications and helpful links

General Publications

• Milman N. Postpartum anemia I: definition, prevalence, causes, and consequences. Ann Hematol. 2011 Nov;90(11):1247-53. doi: 10.1007/s00277-011-1279-z. Epub 2011 Jun 28.
• Dodd J, Dare MR, Middleton P. Treatment for women with postpartum iron deficiency anaemia. Cochrane Database Syst Rev. 2004 Oct 18;2004(4):CD004222. doi: 10.1002/14651858.CD004222.pub2.
• Bhandal N, Russell R. Intravenous versus oral iron therapy for postpartum anaemia. BJOG. 2006 Nov;113(11):1248-52. doi: 10.1111/j.1471-0528.2006.01062.x. Epub 2006 Sep 27.
• Ramakers C, van der Woude DA, Verzijl JM, Pijnenborg JM, van Wijk EM. An added value for the hemoglobin content in reticulocytes (CHr) and the mean corpuscular volume (MCV) in the diagnosis of iron deficiency in postpartum anemic women. Int J Lab Hematol. 2012 Oct;34(5):510-6. doi: 10.1111/j.1751-553X.2012.01423.x. Epub 2012 May 1.
• Breymann C, Honegger C, Holzgreve W, Surbek D. Diagnosis and treatment of iron-deficiency anaemia during pregnancy and postpartum. Arch Gynecol Obstet. 2010 Nov;282(5):577-80. doi: 10.1007/s00404-010-1532-z. Epub 2010 Jun 25.
• Milman N. Postpartum anemia II: prevention and treatment. Ann Hematol. 2012 Feb;91(2):143-54. doi: 10.1007/s00277-011-1381-2. Epub 2011 Dec 9.
• Bergmann RL, Richter R, Bergmann KE, Dudenhausen JW. Prevalence and risk factors for early postpartum anemia. Eur J Obstet Gynecol Reprod Biol. 2010 Jun;150(2):126-31. doi: 10.1016/j.ejogrb.2010.02.030. Epub 2010 Mar 29.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Anticipated): June 1, 2016
• Study Completion (Anticipated): August 1, 2016

Study Registration Dates

• First Submitted: December 31, 2015
• First Submitted That Met QC Criteria: January 13, 2016
• First Posted (Estimate): January 14, 2016

Study Record Updates

• Last Update Posted (Estimate): March 29, 2016
• Last Update Submitted That Met QC Criteria: March 25, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: hemoglobin; Traditional Chinese Medicine; postpartum anemia; iron metabolism; Ejiao
• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia
• Other Study ID Numbers: PA-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No