Clinical Trial Of The Therapeutic Efficacy Of Transamin On Menorrhagia After IUD Insertion

【Backgroud】Intrauterine device(IUD) is an anticonceptive device placed in woman’s uterine cavity,and is a convenient and effective contraceptive method that only affect part of the body.IUD is the most commonly used contraceptive method among Chinese reproductive women.IUD,however,also may cause side effects, especially in relation to bleeding abnormality that is one of the main reasons for IUD discontinuation.Bleeding abnormalities include:increased amount of bleeding, prolonged duration and intermenstrual bleeding,etc.Transamin(tranexamic acid) is one of conventional hemostatic drugs recommended by WHO.It can prevent errhysis and the allergic or inflammatory symptoms caused by errhysis.At present,it already has been used in treatment of hemorrhagic diseases of clinical surgery,gynaecology,obstetrics,blood,tumor,and other domains. Transamin has been used to cure IUD associated abnormal menstruation in Western women while there have been few studies to corroborate this effect in China.【Objectives】To study the efficacy and safety of transamin on menorrhagia after IUD insertion,and compare with the treatment of other conventional drugs,such as vitamin K and Fukeqianjinpian.To evaluate the three treatments of menorrhagia on pharmacoeconomics.【Methods】It is a randomized,control,open and multi-center clinical trial.The blood loss was measured over four consecutive menstrual cycles.The first menstrual cycle after IUD insertion was served as baseline data.During the two subsequent menstrual cycles,each woman was administrated transamin,vitamin K,or Fukeqianjinpian,which was allocated randomly.The drugs prescribed should be taken daily for the first five days of menstruation.In the fourth menstrual cycle,no tablets were prescribed and this cycle was designed to investigate the persistence of efficacy.Each woman need go to designated research center for three times’ follow-up.Transamin group was compared with vitamin K group and Fukeqianjinpian group, respectively.The primary outcome variables include menstrual blood loss[pictorial blood loss assessment chart(PBAC)],menorrhagia cure rate,etc.Other outcome variables include duration of menstruation,menstrual cycle,dysmenorrheal,irregular bleeding,adverse effect,etc.Quality of life was evaluated and pharmacoeconomics analysis was conducted in the clinical trail.Statistical description & statistical inference were carried out using SAS 9.0.【Results】A total of 453 women were recruited for the clinical trial,of which 9 women were lose follow-up at the end of trail.In the first(control) cycle, demographical characteristics,menstrual history,reproductive history,contraceptive history,IUD insertion surgery and main efficacy variables such as PBAC, hemoglobin,RBC,quality of life and quality of menstruation related life between three groups were no statistically different.Both Intent-to-Treat population and Per-Protocol population were used to analyze the primary efficacy of the three drugs.After medication,PBAC consecutively decreased in subsequent three cycles in both population.During the two cycles of medication, there were significant differences of PBAC between the three groups.PBAC of transamin group was lower than the other two groups,and the reduced value of transamin group was two times of each other group.But in the fourth cycle,the PBAC of transamin group was lower than vitamin K group,and had no significant difference with Fukeqianjinpian group.Controlled for potential confounding,the menorrhagia cure rate of transamin group was significant higher than the other two groups,OR in ITT population was 3.027,2.607,respectively.ITT population was used to analyze other outcomes such as duration of menstruation, menstrual cycle length,dysmenorrheal,adverse effect,etc.Duration of menstruation was reduced after medication in all three groups,and the reduced value of transamin group was higher than the other two groups.There was no significant difference of menstrual cycle length between the three groups either before medication or after medication.The incidence of dysmenorrheal was gradually decreased after medication in all three groups,and the severity of dysmenorrheal was also consecutively relieved.Both the incidence of dysmenorrheal and adverse effect between the three groups was no significant difference.ITT population was also used to evaluate the quality of life and pharmacoeconomics analysis.Only transamin group improved the quality of life after medication,other two groups had no significant change.When the menorrhagia cure rate was considered as the effect indicator,the cost-effect ratio(C/E) of three groups was 315.04,134.50,and 173.02,respectively.When increased rate of total score of SF-36 was used to evaluate the efficacy,Fukeqianjinpian was not the best treatment of menorrhagia using cost-mininazition analysis,and the cost-effect ratio(C/E) of transamin and vitamin K was 75.98,191.30,respectively.【Conclusions】Transamin can efficiently reduce menstrual blood loss,duration of menstruation and incidence of menorrhagia after IUD insertion,and it is more effective than vitamin K and Fukeqianjinpian.There is no significant difference between the three drugs on improvement of dysmenorrheal and occurance of adverse effect.Transamin is more effective than vitamin K and Fukeqianjinpian on improving the quality of people’s life who suffer from menorrhagia after IUD insertion.When used the improved rate of quality of life as the effect indicator,the C/E of transamin is better than the other two drugs.But when used the the menorrhagia cure rate as the effect indicator,vitamin K has the better C/E compared with the other two drugs.