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CTRI Number  CTRI/2022/11/047538 [Registered on: 22/11/2022] Trial Registered Prospectively
Last Modified On: 08/11/2022
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Medical Device 
Study Design  Single Arm Study 
Public Title of Study   To study the effect of progesterone hormone containing intra uterine system in women with bleeding diorders  
Scientific Title of Study   Efficacy of levonorgestrel intrauterine system in reducing menstrual blood loss in women with haematological disorders 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Jai Shree 
Designation  Junior resident 
Affiliation  AIIMS New Delhi 
Address  Junior resident Obstetrics and gyanecology AIIMS New Delhi
Department fo obstetrics and Gynecology AIIMS New Delhi
New Delhi
DELHI
110029
India 
Phone  9050268841  
Fax    
Email  jaishreeyadav328@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Garima Kachhawa 
Designation  Additional Professor  
Affiliation  AIIMS New Delhi 
Address  Additional Professor Obstetrics and gyanecology AIIMS New Delhi
AIIMS NEW DELHI
New Delhi
DELHI
110029
India 
Phone  9868246702  
Fax    
Email  garimakachhawa2012@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Jai Shree 
Designation  Junior resident 
Affiliation  AIIMS New Delhi 
Address  Junior resident Obstetrics and gyanecology AIIMS New Delhi
Room number 607 Hostel 19 AIIMS New Delhi
New Delhi
DELHI
110029
India 
Phone  9050268841  
Fax    
Email  jaishreeyadav328@gmail.com  
 
Source of Monetary or Material Support  
AIIMS New Delhi 
 
Primary Sponsor  
Name  AIIMS New Delhi 
Address  AIIMS New Delhi  
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Jai Shree  AIIMS New Delhi   Gynecology and hematology department
New Delhi
DELHI 
9050268841

jaishreeyadav328@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institute ethics committee for post graduate research AIIMS  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: D680||Von Willebrands disease,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  LNG IUS   Patient will be councelled and explained the procedure. Risk banefit of LNG IUS will be told.Patient asked to lie down in lithotomy position and a bimanualexamination will be done to find out the position of uterus. The procedure itself is done with the sterile precautions to avoid any contamination or infection. Perineum and vagina are cleaned with an anti-septic solution. Sims speculum is inserted and cervix is held with valsellum.With the help of sterile uterine sound, the utero-cervical length is measured.Sterile IUD is taken after wearing sterile gloves. Insertor is picked up which is holding IUD. Carefully threads are released from behind the slider, allowing them to hang freely. Ensure that the arms of the device are horizontal. Then pull on both threads to draw the IUD into the insertion tube so that the knobs at the end of the arms cover the open end of the inserter.then insert the IUD by holding at top of handle and places the insertor in cervical canal. Insertor is advanced into the uterus until the flange is 2 cm away from external os.While holding the inserter steady, the arms of the IUD by pulling the slider back until the top of the slider reaches the raised horizontal line on the handle and the insertor is advanced until flange touches cervical cavity. While holding the inserter firmly in position physician then releases the IUD by pulling the slider all the way down. Then insertor is removed from uterus and threads are cut to length of 2-3 cm.If patient perceives pain, oral analgesia is given, 
Comparator Agent  Nil  Nil 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  45.00 Year(s)
Gender  Female 
Details  1. Haematological disorders like coagulation defects and severe anaemia
2. Women on anti coagulant drugs
3. Age more than 18 years
4. Willing to use intrauterine device as a treatment option
5. Willing to participate in study. 
 
ExclusionCriteria 
Details  Uterine pathology of abnormal menstrual bleeding
Mullerian anomalies
Wants to conceive
Vaginal or cervical infection
Undiagnosed irregular vaginal bleeding 
 
Method of Generating Random Sequence   Not Applicable 
Method of Concealment   Not Applicable 
Blinding/Masking   Not Applicable 
Primary Outcome  
Outcome  TimePoints 
To evaluate the efficacy of LNG IUS in reducing menstrual blood flow in women with haematological disorders
Measure- PBAC score 
At 3 months ,6 months post LNG IUS insertion  
 
Secondary Outcome  
Outcome  TimePoints 
1.Evaluate improvement in hemoglobin levels after LNG IUS insertion
2.To evaluate reduction in requirement of anti hemostatic drugs
3.To evaluate reduction ( if any) in frequency of transfusion of blood products
4.To evaluate blood flow changes if any, in uterine artery post insertion of LNG IUS
5.To evaluate improvement in quality of life of women with help of a validated questionnaire. 
1,3,6 months post insertion 
 
Target Sample Size   Total Sample Size="35"
Sample Size from India="35" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   N/A 
Date of First Enrollment (India)   01/12/2022 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="8"
Days="20" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   nil till now 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary   Bleeding disorders affects about 14 % women during their reproductive years. These women may experience abnormal uterine bleeding (AUB) which may be acute or chronic. Heavy menstrual bleeding (HMB) which is defined as excessive bleeding during menses affecting the health of women is one of the most common symptoms in women with bleeding disorders and these women present at an early age as compared to women with AUB without bleeding disorders1.
Acquired or inherited bleeding disorders are diagnosed in 10% to 17% of women presenting with AUB and in 21% to 46% of adolescents with HMB. Almost half of adolescents diagnosed as having a bleeding disorder have had HMB since menarche and 12% have required hospitalization secondary to anemia2 HMB affects around 74-93 % percent of women with underlying inherited bleeding disorders and Von Willebrand Disease(VWD) and around 35-95% of women with platelet disorders or other clotting factor deficiencies3. 
Type 1 VWD is a common type of coagulopathy in women of adolescent age andis responsible for HMB in around 13% of women having HMB.

According to FIGO classification of AUB,(PALM-COIEN), abnormal uterine bleeding due to Coagulopathy or bleeding disorders is classified as AUB-C and comprise women with inherited or acquired bleeding disorders like VWD, thrombocytopenia, platelet function disorders, abnormal platelet factors, and in women on anticoagulation or anti platelet therapy2.Also women with severe anemia are at increased risk of worsening and require blood transfusion due to HMB.

In a survey done in US,79% of women with VWD reported to have HMB and out of these,71% required medical attention for the same, 13 % required hysterectomy as last resort for management of HMB4.Since heavy menstrual bleeding starts at the very onset of menarche and continues throughout reproductive life, the quality of life of these women is severely affected and around 66 % women with bleeding disorder develop iron deficiency anemia, while women with non nutritional anemia require multiple blood transfusions, they are at an increased risk of developing iron‐deficiency anemia.Excessive bleeding every month in these young women may cause significantly low general health, loss of initiative5 and poor quality of life, leading to problems in full participation in school, athletic , social activities and depression 6,7. Further frequent visits to hospital, the cost of treatment for blood and products transfusion adds to considerable financial burden on families of these women.

The aim of treatment in both these group of disorders is complete cessation of menses without causing any adverse systemic effects. Management options for heavy menstrual bleeding in women with bleeding disorders include hormonal treatment like oral or injectable progestins or combined hormonal contraceptives (CHCs), anti-fibrinolytics, desmopressin and iron supplementations8,9,10. Severe bleeding episodes deplete coagulation factors and to control bleeding multiple blood and blood products are transfused which is fraught with its own concerns. 

Oral progestins are used to control acute episode of bleeding and then cyclic progesterone or combined estrogen progesterone pills induces controlled cyclical withdrawal bleedingand reduces the amount of blood flowby 35-69% 11,12. Combined hormonal contraceptivesare considered as first line therapy in women with bleeding disorders however there are compliance issues due to daily administration and several side effects like risk of thrombosis 11.Combined hormonal contraceptiveswhen used over a period of six months reduces blood loss in women with unacceptable HMB from 12% to 77%13  and authors also reached to the conclusion that LNG IUS lead to reduction in mean blood loss in 83 % women in comparison to combined hormonal contraceptives which was 68% only13.Adherence to treatment options which needs to be taken daily, weekly or monthly seem to pose a great challenge in compliance among adolescents. Since this therapy would have to be initiated early in life and continued for a reasonably long time, it is essential that both the efficacy and safety be evidence‐based. Further, surgical option of endometrial ablation and hysterectomy are not an option in these young girls.

The safety and efficacy of LNG-IUS for treatment of AUB in peri menopausal women is welldemonstrated. LNG intra-uterine system causes a significant reduction in menstrual blood loss by and is effectively used as an alternative to surgery for treatment of HMB in reproductive age women. It reduces menstrual blood loss by 97% at 12 months of use14,15. Once inserted it is effective for 5 years and in most of the users causes amenorrhea. LNG IUS is being used in women with bleeding disorders however the data on the use of LNG IUS in young women with bleeding disorders is scarce3. Although LNG IUS is recommended as first line management for other causes of AUB however in AUB-C it is still recommended as second-line treatment of choice that is, where combined oral contraceptive pill is contraindicated, LNG-IUS is preferred as first-line treatment11.  In 2011 a review of case series of women with inherited blood disorders who have been using LNG IUS has shown that it is an effective long-term treatment for HMB in these women3



The available treatment modalities though proven effective, their associated side effects, limited efficacy and the poor compliance led to discontinuation, and this necessitate the requisite for alternative ‘fit and forget’ methods like levonorgestrel-releasing intrauterine system (LNG-IUS)
Hence this study becomes important in a developing country like India where this problem is quite prevalent and requirement in blood banks for transfusion is very high significantly in such adolescent women with underlying bleeding disorders.So, with the intention to add the data to already existing data on efficacy of LNG IUS in women with hematological disorders, this study has been planned.Bleeding disorders affects about 14 % women during their reproductive years. These women may experience abnormal uterine bleeding (AUB) which may be acute or chronic. Heavy menstrual bleeding (HMB) which is defined as excessive bleeding during menses affecting the health of women is one of the most common symptoms in women with bleeding disorders and these women present at an early age as compared to women with AUB without bleeding disorders1.
Acquired or inherited bleeding disorders are diagnosed in 10% to 17% of women presenting with AUB and in 21% to 46% of adolescents with HMB. Almost half of adolescents diagnosed as having a bleeding disorder have had HMB since menarche and 12% have required hospitalization secondary to anemia2 HMB affects around 74-93 % percent of women with underlying inherited bleeding disorders and Von Willebrand Disease(VWD) and around 35-95% of women with platelet disorders or other clotting factor deficiencies3. 
Type 1 VWD is a common type of coagulopathy in women of adolescent age andis responsible for HMB in around 13% of women having HMB.

According to FIGO classification of AUB,(PALM-COIEN), abnormal uterine bleeding due to Coagulopathy or bleeding disorders is classified as AUB-C and comprise women with inherited or acquired bleeding disorders like VWD, thrombocytopenia, platelet function disorders, abnormal platelet factors, and in women on anticoagulation or anti platelet therapy2.Also women with severe anemia are at increased risk of worsening and require blood transfusion due to HMB.

In a survey done in US,79% of women with VWD reported to have HMB and out of these,71% required medical attention for the same, 13 % required hysterectomy as last resort for management of HMB4.Since heavy menstrual bleeding starts at the very onset of menarche and continues throughout reproductive life, the quality of life of these women is severely affected and around 66 % women with bleeding disorder develop iron deficiency anemia, while women with non nutritional anemia require multiple blood transfusions, they are at an increased risk of developing iron‐deficiency anemia.Excessive bleeding every month in these young women may cause significantly low general health, loss of initiative5 and poor quality of life, leading to problems in full participation in school, athletic , social activities and depression 6,7. Further frequent visits to hospital, the cost of treatment for blood and products transfusion adds to considerable financial burden on families of these women.

The aim of treatment in both these group of disorders is complete cessation of menses without causing any adverse systemic effects. Management options for heavy menstrual bleeding in women with bleeding disorders include hormonal treatment like oral or injectable progestins or combined hormonal contraceptives (CHCs), anti-fibrinolytics, desmopressin and iron supplementations8,9,10. Severe bleeding episodes deplete coagulation factors and to control bleeding multiple blood and blood products are transfused which is fraught with its own concerns. 

Oral progestins are used to control acute episode of bleeding and then cyclic progesterone or combined estrogen progesterone pills induces controlled cyclical withdrawal bleedingand reduces the amount of blood flowby 35-69% 11,12. Combined hormonal contraceptivesare considered as first line therapy in women with bleeding disorders however there are compliance issues due to daily administration and several side effects like risk of thrombosis 11.Combined hormonal contraceptiveswhen used over a period of six months reduces blood loss in women with unacceptable HMB from 12% to 77%13  and authors also reached to the conclusion that LNG IUS lead to reduction in mean blood loss in 83 % women in comparison to combined hormonal contraceptives which was 68% only13.Adherence to treatment options which needs to be taken daily, weekly or monthly seem to pose a great challenge in compliance among adolescents. Since this therapy would have to be initiated early in life and continued for a reasonably long time, it is essential that both the efficacy and safety be evidence‐based. Further, surgical option of endometrial ablation and hysterectomy are not an option in these young girls.

The safety and efficacy of LNG-IUS for treatment of AUB in peri menopausal women is welldemonstrated. LNG intra-uterine system causes a significant reduction in menstrual blood loss by and is effectively used as an alternative to surgery for treatment of HMB in reproductive age women. It reduces menstrual blood loss by 97% at 12 months of use14,15. Once inserted it is effective for 5 years and in most of the users causes amenorrhea. LNG IUS is being used in women with bleeding disorders however the data on the use of LNG IUS in young women with bleeding disorders is scarce3. Although LNG IUS is recommended as first line management for other causes of AUB however in AUB-C it is still recommended as second-line treatment of choice that is, where combined oral contraceptive pill is contraindicated, LNG-IUS is preferred as first-line treatment11.  In 2011 a review of case series of women with inherited blood disorders who have been using LNG IUS has shown that it is an effective long-term treatment for HMB in these women3



The available treatment modalities though proven effective, their associated side effects, limited efficacy and the poor compliance led to discontinuation, and this necessitate the requisite for alternative ‘fit and forget’ methods like levonorgestrel-releasing intrauterine system (LNG-IUS)
Hence this study becomes important in a developing country like India where this problem is quite prevalent and requirement in blood banks for transfusion is very high significantly in such adolescent women with underlying bleeding disorders.So, with the intention to add the data to already existing data on efficacy of LNG IUS in women with hematological disorders, this study has been planned
 
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