Ignite Creation Date:
2024-05-06 @ 3:59 PM
Last Modification Date:
2024-10-26 @ 2:01 PM
Study NCT ID:
NCT04832906
Status:
COMPLETED
Last Update Posted:
2021-04-06
First Post:
2021-04-01
Brief Title:
UA Versus UAE in Treatment of Fibroids
Sponsor:
Ain Shams Maternity Hospital
Organization:
Ain Shams Maternity Hospital
Study Overview
Official Title:
Ulipristal Acetate Therapy Versus Uterine Artery Embolization in Management of Uterine Fibroids
Status:
COMPLETED
Status Verified Date:
2021-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Study objective To prove that Ulipristal acetate is an effective line of management for uterine fibroids by causing a significant decline in fibroid volumes resulting in a substantial relief of fibroid-related symptoms and to compare its results with those of uterine artery embolization
Design A randomized control trial Setting Maternity Hospital Ain Shams University
Patients Women with symptomatic uterine fibroids
Interventions 70 women were randomly assigned to either Ulipristal Acetate UA group or uterine artery embolization UAE group 35 in each group Both groups were followed up to detect the decline in fibroid size as well as the improvement of symptoms
Design A randomized control trial Setting Maternity Hospital Ain Shams University
Patients Women with symptomatic uterine fibroids
Interventions 70 women were randomly assigned to either Ulipristal Acetate UA group or uterine artery embolization UAE group 35 in each group Both groups were followed up to detect the decline in fibroid size as well as the improvement of symptoms
Detailed Description:
Inclusion Criteria
Women with symptomatic uterine fibroids were recruited into the study after fulfilling the following criteria
Their age should range from 35 to 50 years
Their body mass index BMI should range from 18 to 35 Kgm2
The presence of multiple symptomatic type 2 3 4 5 or 6 uterine fibroids according to the FIGO classification
The dominant fibroid diameter should range from 4 to 8 cm as assessed by ultrasound
They should not be seeking future fertility
They should be refusing any surgical intervention whether myomectomy or hysterectomy
Exclusion Criteria
1 Post-menopausal status or premature ovarian failure
2 Type 0 1 and 7 uterine fibroids according to FIGO classification
3 Previous myomectomy or any uterine surgery
4 Previous or ongoing hormonal treatment
Sampling Method
The study sample will be a convenient sample where women fulfilling the inclusion criteria and consenting to participate in the study will be recruited
Sample Size justification
The study will include 70 women with symptomatic uterine fibroids who will be randomized into two groups with 35 women in each group
The required sample size has been calculated using the PASS 15 Power Anal-ysis and Sample Size Software PASS version 15 2017 NCSS LLC Kaysville Utah USA
The main outcome measure is the reduction in fibroid volume The secondary outcome measures are symptoms relief and improvement in quality of life
A previous study reported that Ulipristal Acetate UA was comparable to uterine artery embolization UAE as regards the percentage of reduction in fibroid volume with median interquartile range percentage reduction of 481 248 - 66 versus 473 295 - 695 for UPA and UAE respectively Czuczwar et al 2015
Using the methods described by Wan et al 2014 and Luo et al 2018 we calculated that the mean SD percentage of reduction in fibroid volume was 440 285 versus 489 323 for UPA and UAE respectively with mean difference of 49 and common within group SD of 305
Taking into consideration a drop-out rate of about 10 due to loss of follow up or withdrawal from the study it is estimated that a sample size of 35 patients per group achieves 80 power using a one-sided equivalence test with a significance level of 5 alpha-error 005 when the difference between the two means is 49 common within group SD is 305 and equivalence limits are -25 and 25
On the other hand this sample size achieves a power of 82 to detect a statistically significant difference between the two groups as regards the symptoms scores and measures of ovarian reserve AFC and AMH for an effect size equivalent to a Cohens d of 075 ie 075 common SD using a two-sided unpaired t-test with the same significance level of alpha 005
These equivalence limits and effect size have been targeted as they may be considered clinically important
Informed consent
The nature and scope of the clinical study will be explained in an understand-able way to the patients and an informed consent form in Arabic language including all the study procedures advantages and possible risks and specifying who informed the patient will be provided and the patient must sign on it before participation The study protocol and patient informed consent will be reviewed and approved by the Ethics Committee of the Obstetrics and Gynecology Department Ain Shams University
Funding
This study will be funded by the researcher himself and Ain Shams University
Randomization and Allocation concealment
The participants will be randomly assigned into one of the two study groups using a computer random sequence generator The randomization will be made using sequentially numbered opaque sealed envelopes each envelope contains the method of intervention according to the random sequence and will be opened just before the intervention
Study Procedures
All participants will undergo full assessment before starting either treatment options This assessment will include
Detailed History
Personal history including patients full name age marital status parity occupation and residence will be recorded
Menstrual history including age of menarche DC amount of menstrual flow and associated dysmenorrhea
Contraceptive history to exclude other causes for uterine bleeding
Past medical history of Diabetes Mellitus hypertension bronchial asthma cardiac diseases anemia etc
Past surgical history of uterine surgeries
History of present illness with detailed analysis of each patients complaint whether abnormal uterine bleeding dysmenorrhea and pelvic pressure symptoms such as urinary urgency or constipation
Physical Examination
General examination including Pulse blood pressure temperature body mass index BMI auscultation of lungs and heart and complex-ion as pallor due to anemia caused by heavy bleeding
Abdominal examination inspection for any scar palpation of the abdomen for any tenderness and for pelviabdominal masses
Pelvic examination complete bimanual examination for uterine size mobility and palpable uterine fibroids
Investigations
Baseline hemoglobin hematocrit and blood grouping
Blood chemistry AST ALT serum creatinine and RBS
Trans-vaginal ultrasound for uterine volume and fibroid location volume and maximum diameter Uterine volume expressed in cubic centimeters will be calculated by measuring the maximum length antero-posterior and transverse diameters of the uterine corpus using the US device software formula for calculation of the uterine volume Myoma volumes will be measured by using the existing 2-dimensional US methods The FIGO classification system figure 1 will be used for defining the myoma location
Study groups
Patients recruited in this study will be randomized into one of the following study groups
1 Group A Ulipristal Acetate UA - Fibristal group n35
Patients within this group will receive oral Ulipristal Acetate Fibristal 5 mg day starting from the first day of menstrual bleeding and for 3 months period of the study
2 Group B Uterine artery embolization UAE group n35
Patients within this group will undergo bilateral selective uterine artery embolization during which polyvinyl alcohol PVA particles will be administered via a catheter followed by capping with a plug of gelatin sponge The end point for embolization is to have a static column of contrast in the uterine artery with only a stump filling when the internal iliac artery was injected The gelatin sponge cap was thought to both complete the occlusion of the uterine artery and to prevent PVA particles from being drawn out of the uterine artery by the Venturi effect which would result in non-target embolization
Follow up
Each patient within both groups will be subjected to follow-up trans-vaginal ultrasound US 3 months after Ulipristal acetate UA therapy or after uterine artery embolization UAE session to detect the decline in uterine fibroid volumes in comparison to their baseline To reduce inter-observer variability associated with ultrasound imaging measurements will be always taken by the same sonographer
Each patient within both groups will be evaluated clinically for the symptoms reported at least 1 month before starting the treatment baseline and 3 months after Ulipristal acetate UA therapy or after uterine artery embolization UAE session Durability of the used treatment line will be tested by follow up after one year from initiating therapy
Fibroid-related heavy menstrual bleeding HMB will be evaluated by the pictorial blood assessment chart score figure 2 This instrument is a self-administered pictorial chart that takes account of the number of sanitary pads and tampons used presence of blood clots and episodes of bleeding The 1-month pictorial blood assessment chart score was calculated from the addition of daily scores for 28 days A score of higher than 100 during the first 8 days of menstruation will be defined as heavy menstrual bleeding HMB
Subjective feelings of pelvic pressure urinary urgency and constipation will be recorded on a simplified questionnaire containing 2 categories defined as absent and present The visual analog scale VAS pain score figure 3 will be used to determine the presence or absence of pelvic pain
Statistical Methods
Data will be analyzed using Intention to treat ITT analysis According to Fisher et al 1990 the ITT analysis includes all randomized patients in the groups to which they were randomly assigned regardless of their adherence with the entry criteria regardless of the treatment they actually received and regardless of subsequent withdrawal from treatment or deviation from the protocol
In other words ITT analysis includes every subject who is randomized according to randomized treatment assignment It ignores non-compliance protocol deviations withdrawal and anything that happens after randomization ITT analysis is usually described as once randomized always analyzed
ITT analysis avoids overoptimistic estimates of the efficacy of one of the two interventions resulting from the removal of non-compliers by accepting that noncompliance and protocol deviations are likely to occur in actual clinical practice
Efficacy of the two study interventions will be compared using Odds ratio OR Relative risk RR Number needed to treat NNT and Number needed to harm NNH
Data will be analyzed using IBM SPSS Statistics version 23 IBM Corp Armonk NY Normally distributed numerical data will be presented as mean and SD and skewed data as median and interquartile range Qualitative data will be presented as number and percentage Normally distributed numerical data will be compared using the unpaired t test and skewed data using the Mann-Whitney test Categorical data will be compared using the Pearson chi-squared test or Fishers exact test if appropriate A two-sided p-value 005 will be considered statistically significant
Women with symptomatic uterine fibroids were recruited into the study after fulfilling the following criteria
Their age should range from 35 to 50 years
Their body mass index BMI should range from 18 to 35 Kgm2
The presence of multiple symptomatic type 2 3 4 5 or 6 uterine fibroids according to the FIGO classification
The dominant fibroid diameter should range from 4 to 8 cm as assessed by ultrasound
They should not be seeking future fertility
They should be refusing any surgical intervention whether myomectomy or hysterectomy
Exclusion Criteria
1 Post-menopausal status or premature ovarian failure
2 Type 0 1 and 7 uterine fibroids according to FIGO classification
3 Previous myomectomy or any uterine surgery
4 Previous or ongoing hormonal treatment
Sampling Method
The study sample will be a convenient sample where women fulfilling the inclusion criteria and consenting to participate in the study will be recruited
Sample Size justification
The study will include 70 women with symptomatic uterine fibroids who will be randomized into two groups with 35 women in each group
The required sample size has been calculated using the PASS 15 Power Anal-ysis and Sample Size Software PASS version 15 2017 NCSS LLC Kaysville Utah USA
The main outcome measure is the reduction in fibroid volume The secondary outcome measures are symptoms relief and improvement in quality of life
A previous study reported that Ulipristal Acetate UA was comparable to uterine artery embolization UAE as regards the percentage of reduction in fibroid volume with median interquartile range percentage reduction of 481 248 - 66 versus 473 295 - 695 for UPA and UAE respectively Czuczwar et al 2015
Using the methods described by Wan et al 2014 and Luo et al 2018 we calculated that the mean SD percentage of reduction in fibroid volume was 440 285 versus 489 323 for UPA and UAE respectively with mean difference of 49 and common within group SD of 305
Taking into consideration a drop-out rate of about 10 due to loss of follow up or withdrawal from the study it is estimated that a sample size of 35 patients per group achieves 80 power using a one-sided equivalence test with a significance level of 5 alpha-error 005 when the difference between the two means is 49 common within group SD is 305 and equivalence limits are -25 and 25
On the other hand this sample size achieves a power of 82 to detect a statistically significant difference between the two groups as regards the symptoms scores and measures of ovarian reserve AFC and AMH for an effect size equivalent to a Cohens d of 075 ie 075 common SD using a two-sided unpaired t-test with the same significance level of alpha 005
These equivalence limits and effect size have been targeted as they may be considered clinically important
Informed consent
The nature and scope of the clinical study will be explained in an understand-able way to the patients and an informed consent form in Arabic language including all the study procedures advantages and possible risks and specifying who informed the patient will be provided and the patient must sign on it before participation The study protocol and patient informed consent will be reviewed and approved by the Ethics Committee of the Obstetrics and Gynecology Department Ain Shams University
Funding
This study will be funded by the researcher himself and Ain Shams University
Randomization and Allocation concealment
The participants will be randomly assigned into one of the two study groups using a computer random sequence generator The randomization will be made using sequentially numbered opaque sealed envelopes each envelope contains the method of intervention according to the random sequence and will be opened just before the intervention
Study Procedures
All participants will undergo full assessment before starting either treatment options This assessment will include
Detailed History
Personal history including patients full name age marital status parity occupation and residence will be recorded
Menstrual history including age of menarche DC amount of menstrual flow and associated dysmenorrhea
Contraceptive history to exclude other causes for uterine bleeding
Past medical history of Diabetes Mellitus hypertension bronchial asthma cardiac diseases anemia etc
Past surgical history of uterine surgeries
History of present illness with detailed analysis of each patients complaint whether abnormal uterine bleeding dysmenorrhea and pelvic pressure symptoms such as urinary urgency or constipation
Physical Examination
General examination including Pulse blood pressure temperature body mass index BMI auscultation of lungs and heart and complex-ion as pallor due to anemia caused by heavy bleeding
Abdominal examination inspection for any scar palpation of the abdomen for any tenderness and for pelviabdominal masses
Pelvic examination complete bimanual examination for uterine size mobility and palpable uterine fibroids
Investigations
Baseline hemoglobin hematocrit and blood grouping
Blood chemistry AST ALT serum creatinine and RBS
Trans-vaginal ultrasound for uterine volume and fibroid location volume and maximum diameter Uterine volume expressed in cubic centimeters will be calculated by measuring the maximum length antero-posterior and transverse diameters of the uterine corpus using the US device software formula for calculation of the uterine volume Myoma volumes will be measured by using the existing 2-dimensional US methods The FIGO classification system figure 1 will be used for defining the myoma location
Study groups
Patients recruited in this study will be randomized into one of the following study groups
1 Group A Ulipristal Acetate UA - Fibristal group n35
Patients within this group will receive oral Ulipristal Acetate Fibristal 5 mg day starting from the first day of menstrual bleeding and for 3 months period of the study
2 Group B Uterine artery embolization UAE group n35
Patients within this group will undergo bilateral selective uterine artery embolization during which polyvinyl alcohol PVA particles will be administered via a catheter followed by capping with a plug of gelatin sponge The end point for embolization is to have a static column of contrast in the uterine artery with only a stump filling when the internal iliac artery was injected The gelatin sponge cap was thought to both complete the occlusion of the uterine artery and to prevent PVA particles from being drawn out of the uterine artery by the Venturi effect which would result in non-target embolization
Follow up
Each patient within both groups will be subjected to follow-up trans-vaginal ultrasound US 3 months after Ulipristal acetate UA therapy or after uterine artery embolization UAE session to detect the decline in uterine fibroid volumes in comparison to their baseline To reduce inter-observer variability associated with ultrasound imaging measurements will be always taken by the same sonographer
Each patient within both groups will be evaluated clinically for the symptoms reported at least 1 month before starting the treatment baseline and 3 months after Ulipristal acetate UA therapy or after uterine artery embolization UAE session Durability of the used treatment line will be tested by follow up after one year from initiating therapy
Fibroid-related heavy menstrual bleeding HMB will be evaluated by the pictorial blood assessment chart score figure 2 This instrument is a self-administered pictorial chart that takes account of the number of sanitary pads and tampons used presence of blood clots and episodes of bleeding The 1-month pictorial blood assessment chart score was calculated from the addition of daily scores for 28 days A score of higher than 100 during the first 8 days of menstruation will be defined as heavy menstrual bleeding HMB
Subjective feelings of pelvic pressure urinary urgency and constipation will be recorded on a simplified questionnaire containing 2 categories defined as absent and present The visual analog scale VAS pain score figure 3 will be used to determine the presence or absence of pelvic pain
Statistical Methods
Data will be analyzed using Intention to treat ITT analysis According to Fisher et al 1990 the ITT analysis includes all randomized patients in the groups to which they were randomly assigned regardless of their adherence with the entry criteria regardless of the treatment they actually received and regardless of subsequent withdrawal from treatment or deviation from the protocol
In other words ITT analysis includes every subject who is randomized according to randomized treatment assignment It ignores non-compliance protocol deviations withdrawal and anything that happens after randomization ITT analysis is usually described as once randomized always analyzed
ITT analysis avoids overoptimistic estimates of the efficacy of one of the two interventions resulting from the removal of non-compliers by accepting that noncompliance and protocol deviations are likely to occur in actual clinical practice
Efficacy of the two study interventions will be compared using Odds ratio OR Relative risk RR Number needed to treat NNT and Number needed to harm NNH
Data will be analyzed using IBM SPSS Statistics version 23 IBM Corp Armonk NY Normally distributed numerical data will be presented as mean and SD and skewed data as median and interquartile range Qualitative data will be presented as number and percentage Normally distributed numerical data will be compared using the unpaired t test and skewed data using the Mann-Whitney test Categorical data will be compared using the Pearson chi-squared test or Fishers exact test if appropriate A two-sided p-value 005 will be considered statistically significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None