Tranexamic Acid (TA) vs Combined Oral Contraceptive (COCP) Pilot Study

• Sponsor: Baylor College of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01428713
• Collaborator: (none)
• Enrollment: 17
• Location: 1
• Arms: 2
• Duration (Months): 22
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

Menorrhagia, considered a public health challenge and reported by 5 to 10% of adult women, is encountered even more frequently in adolescents. Surveys of school students in the United States (US) and Europe reported menorrhagia in 37% to 55% of adolescent females. Medical management of adolescent menorrhagia includes various formulations of hormonal therapy and the antifibrinolytic agent epsilon aminocaproic acid. Oral tranexamic acid (TA), a more potent antifibrinolytic agent used as standard therapy for menorrhagia in adult women and in adolescent women in Europe and Canada, was not previously available in the US. Subsequent to US FDA approval in November 2009 of a novel oral TA formulation to treat cyclic heavy menstrual bleeding in adult women, this medication is currently included in the treatment armamentarium for adult menorrhagia. There is currently no preliminary data available in the US about the clinical use of oral TA in an exclusive adolescent population with menorrhagia. Oral contraceptive pills (OCP) are considered standard therapy in the management of menorrhagia in teen-aged women. Oral TA has been shown to be more efficacious than progesterone-only hormonal therapy for menorrhagia in adult women. However, there is no data available comparing the efficacy of oral TA and combined OCP (COCP) in adult women or in adolescents with menorrhagia.

The study hypothesis is that, in adolescent menorrhagia, oral TA will have comparable efficacy in reducing menstrual blood loss (MBL) and improving quality of life (QOL) when compared to the commonly prescribed COCP.

This hypothesis was tested by comparing the efficacy of these two medications, in a prospective randomized crossover trial in post-menarchal young girls with menorrhagia.

Condition or Disease	Intervention/Treatment	Phase
Menorrhagia	Drug: Oral tranexamic acid; Drug: Oral Contraceptive Pills	N/A

Detailed Description

Subjects were randomized to one of two groups (group A or B).

Group A received oral tranexamic acid at 1300 mg (two 650mg tablets), three times each day on days 1 to 5 of menstrual cycle for 3 cycles.

Group B received combined oral contraceptive pills (OCP) with 3 weeks of hormonal pills and 1 week of placebo for 3 cycles.

After 3 cycles of therapy, both groups had one cycle without any therapy. Then, the groups crossed over. Group A, who first received TA, then received OCP. Group B, who first received OCP, then received TA.

All subjects were to receive both tranexamic acid and oral contraceptive pills.

There were a total of 3 study-associated visits per patient: 1 at baseline and 2 at the end of 3 cycles on each medication. These visits were considered within standard of care, as subjects with menorrhagia have frequent monitoring until the effectiveness of the treatment is determined.

At the study visits the following were done:

1. Assessment of the last menstrual period (amount of blood lost) using the Pictorial Blood Assessment Chart (PBAC) score and the number of days the period lasted

2. Quality of Life evaluation - by the patient completing a standardized pediatric quality of life (PedsQL) questionnaire

3. Detailed history and physical examination to evaluate for drug side effects and to look for signs of blood clots.

4. Blood drawn for a complete blood count.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective Crossover Trial of Oral Tranexamic Acid and Combined Oral Contraceptive in Adolescents With Menorrhagia - A Pilot Study
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group A-Oral tranexamic acid Group A received oral tranexamic acid at 1300 mg (two 650mg tablets), three times each day on days 1 to 5 of menstrual cycle for 3 cycles.	Drug: Oral tranexamic acid; Group A received oral tranexamic acid at 1300 mg (two 650mg tablets), three times each day on days 1 to 5 of menstrual cycle for 3 cycles.
Active Comparator: Group B-Combined oral contraceptive pills Group B received combined oral contraceptive pills with 3 weeks of hormonal pills and 1 week of placebo for 3 cycles.	Drug: Oral Contraceptive Pills; Group B received combined oral contraceptive pills with 3 weeks of hormonal pills and 1 week of placebo for 3 cycles.

Outcome Measures

Primary Outcome Measures

1. To Assess the Efficacy of Oral TA and COCP in Adolescents With Menorrhagia. [Baseline, 3 cycles]

   To assess change in Pictorial Blood Assessment Chart Score (PBAC Score) from baseline to the end of 3 cycles of TA change in quality of life (QOL) as evaluated by the PedsQL instrument from baseline to the end of 3 cycles of TA change in Pictorial Blood Assessment Chart Score (PBAC Score) from baseline to the end of 3 cycles of COCP change in quality of life (QOL) as evaluated by the PedsQL instrument from baseline to the end of 3 cycles of COCP PBAC score: Quantitative score to measure menstrual blood loss. Scale range: Minimum - 0 score, Maximum: No maximum Interpretation: Score > 100 indicates heavy menstrual bleeding Peds QL score: Score to measure quality of life in children Scale range: Minimum: 0, Maximum 100 Calculation: Subscales are reverse scored (using formula 100 - a x 25) and then all subscales are averaged Eg: Subscale score of 3 is reverse scored as: 100 - (3 x 25) = 25 Interpretation: Higher score indicates better quality of life

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 21 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Menstruating females with menorrhagia or menometrorrhagia referred to hematology or gynecology clinics at Texas Childrens Hospital. Menorrhagia is defined as regular periods with heavy menstrual bleeding with a PBAC score greater than 100; menometrorrhagia is heavy vaginal bleeding occurring at irregular intervals.

2. PBAC Score greater than 100 for 2 consecutive cycles

3. Pelvic ultrasound that excludes pelvic pathology that can cause menorrhagia within 12 months prior to study participation.

4. Normal external genitalia examination within 6 months prior to study participation.

5. Normal thyroid stimulating hormone (TSH) in the last 6 months prior to study participation.

6. Negative urine or serum pregnancy test within 4 weeks prior to study participation.

Exclusion Criteria:

1. Presence of intra uterine device.

2. Presence of a diagnosed bleeding disorder based on the standard work-up including complete blood count (CBC), prothrombin time, partial thromboplastin time, fibrinogen, von Willebrand panel and platelet function analysis (PFA-100) or platelet aggregation.

3. Intake of medications with increased risk of bleeding

4. Taking herbal products.

5. Sexually active status.

6. Body weight less than 40 kg.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Baylor College of Medicine	Houston	Texas	United States	77030

Sponsors and Collaborators

• Baylor College of Medicine

Investigators

• Principal Investigator: Lakshmi Srivaths, MD, Baylor College of Medicine/TCH

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lakshmi Srivaths, Principal Investigator, Baylor College of Medicine
• ClinicalTrials.gov Identifier: NCT01428713
• Other Study ID Numbers: H-27934 TA vs COCP Study
• First Posted: Sep 5, 2011
• Last Update Posted: Aug 10, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Lakshmi Srivaths, Principal Investigator, Baylor College of Medicine: menorrhagia; oral contraceptives; oral tranexamic acid
• Additional relevant MeSH terms: Menorrhagia; Tranexamic Acid; Contraceptive Agents; Contraceptives, Oral; Contraceptives, Oral, Combined

Study Results

Participant Flow

Recruitment Details	Post-menarchal young girls </= 21 years of age with menorrhagia or menometrorrhagia, referred to hematology or gynecology clinics at Texas Children's Hospital (TCH) formed the study population.
Pre-assignment Detail	The study design employed was a randomized crossover trial comparing the use of oral TA formulation Lysteda and the COCP formulation Lo/Ovral. Patients were randomized to one of two treatment groups, group A versus group B. Patients who were already on COCP underwent one cycle washout prior to randomization.

Arm/Group Title	Group A: TA First, Then COCP	Group B: COCP First, Then TA
Arm/Group Description	Patients received oral TA (given according to US FDA label for adult women, an off-label use for adolescents <18 years of age) at 1300 mg (two 650mg tablets) three times each day on days 1 to 5 of menstrual cycle for 3 consecutive cycles. Subsequently, patients who initially received TA, received COCP. COCP formulation Lo/Ovral (components: Ethinyl estradiol 30 mcg and norgestrel 0.3 mg; each monthly pack containing 21 hormonal tablets and 7 inactive tablets). Patients received COCP with 3 weeks of hormonal pills and 1 week of placebo pills for 3 consecutive cycles. Each medication was prescribed for 3 menstrual cycles with a 1 month wash out in-between TA and COCP.	Patients received COCP first. COCP formulation Lo/Ovral (components: Ethinyl estradiol 30 mcg and norgestrel 0.3 mg; each monthly pack containing 21 hormonal tablets and 7 inactive tablets). Patients received COCP with 3 weeks of hormonal pills and 1 week of placebo pills for 3 consecutive cycles. Each medication was prescribed for 3 menstrual cycles with a 1 month wash out in-between COCP and TA. Subsequently, patients who initially received COCP, received TA. Patients received oral TA (given according to US FDA label for adult women, an off-label use for adolescents <18 years of age) at 1300 mg (two 650mg tablets) three times each day on days 1 to 5 of menstrual cycle for 3 consecutive cycles.
Period Title: Overall Study
STARTED	9	8
COMPLETED	6	3
NOT COMPLETED	3	5

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Group A: TA first, then COCP: Patients received oral TA (given according to US FDA label for adult women, an off-label use for adolescents <18 years of age) at 1300 mg (two 650mg tablets) three times each day on days 1 to 5 of menstrual cycle for 3 consecutive cycles. Subsequently, patients who initially received TA, received COCP. Group B: COCP first, then TA: Patients received COCP first. COCP formulation Lo/Ovral (components: Ethinyl estradiol 30 mcg and norgestrel 0.3 mg; each monthly pack containing 21 hormonal tablets and 7 inactive tablets). Patients received COCP with 3 weeks of hormonal pills and 1 week of placebo pills for 3 consecutive cycles. Each medication was prescribed for 3 menstrual cycles with a 1 month wash out in-between TA and COCP. Subsequently, patients who initially received COCP, received TA.
Overall Participants	17
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	14.2 (1.6)
Age (Count of Participants)
<=18 years	17 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	17 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	17 100%

Outcome Measures

1. Primary Outcome

Title	To Assess the Efficacy of Oral TA and COCP in Adolescents With Menorrhagia.
Description	To assess change in Pictorial Blood Assessment Chart Score (PBAC Score) from baseline to the end of 3 cycles of TA change in quality of life (QOL) as evaluated by the PedsQL instrument from baseline to the end of 3 cycles of TA change in Pictorial Blood Assessment Chart Score (PBAC Score) from baseline to the end of 3 cycles of COCP change in quality of life (QOL) as evaluated by the PedsQL instrument from baseline to the end of 3 cycles of COCP PBAC score: Quantitative score to measure menstrual blood loss. Scale range: Minimum - 0 score, Maximum: No maximum Interpretation: Score > 100 indicates heavy menstrual bleeding Peds QL score: Score to measure quality of life in children Scale range: Minimum: 0, Maximum 100 Calculation: Subscales are reverse scored (using formula 100 - a x 25) and then all subscales are averaged Eg: Subscale score of 3 is reverse scored as: 100 - (3 x 25) = 25 Interpretation: Higher score indicates better quality of life
Time Frame	Baseline, 3 cycles

Outcome Measure Data

Analysis Population Description

10 patients completed TA and their results were analyzed. 11 patients completed COCP and their results were analyzed.

Arm/Group Title	Group: TA	Group: COCP
Arm/Group Description	Patients received oral TA (given according to US FDA label for adult women, an off-label use for adolescents <18 years of age) at 1300 mg (two 650mg tablets) three times each day on days 1 to 5 of menstrual cycle for 3 consecutive cycles.	Patients received COCP formulation Lo/Ovral (components: Ethinyl estradiol 30 mcg and norgestrel 0.3 mg; each monthly pack containing 21 hormonal tablets and 7 inactive tablets). Patients received COCP with 3 weeks of hormonal pills and 1 week of placebo pills for 3 consecutive cycles.
Measure Participants	10	11
PBAC (Pictorial Blood Assessment Chart) score	536.4 (162.12)	430.6 (157.35)
Peds QL (Pediatric Quality of Life) score	15.6 (5.08)	16.75 (4.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group: TA
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments	P value < 0.05 is considered significant in this study
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	536.4
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 162.12
	Estimation Comments	Comparing PBAC score value at baseline vs. end of 3 cycles for TA

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group: COCP
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments	P value < 0.05 is considered significant for this study
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	430.6
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 157.35
	Estimation Comments	Comparing PBAC score value at baseline vs. end of 3 cycles for COCP

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group: TA
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments	P value < 0.05 is considered significant for this study
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	15.6
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.08
	Estimation Comments	Comparing Peds QL score value at baseline vs. end of 3 cycles for TA

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Group: COCP
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	16.75
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.87
	Estimation Comments	Comparing Peds QL score value at baseline vs. end of 3 cycles for COCP

Adverse Events

Time Frame	8 months
Adverse Event Reporting Description	Only patients that completed each intervention were considered at risk. 10 patients completed TA and their results were analyzed. 11 patients completed COCP and their results were analyzed.
Arm/Group Title	Tranexamic Acid (TA)		Combined Oral Contraceptives (COCP)
Arm/Group Description	Patients received oral tranexamic acid at 1300 mg three times each day on days 1 to 5 of menstrual cycle for 3 cycles. The mean age of the study population was 14.2 years. Patients received oral TA (given according to US FDA label for adult women, an off-label use for adolescents <18 years of age) at 1300 mg (two 650mg tablets) three times each day on days 1 to 5 of menstrual cycle for 3 consecutive cycles. Subsequently, patients who initially received TA, received COCP and patients who initially received COCP, then received TA.		COCP formulation Lo/Ovral (components: Ethinyl estradiol 30 mcg and norgestrel 0.3 mg; each monthly pack containing 21 hormonal tablets and 7 inactive tablets). Patients received COCP with 3 weeks of hormonal pills and 1 week of placebo pills for 3 consecutive cycles. Each medication was prescribed for 3 menstrual cycles with a 1 month wash out in-between medications.
All Cause Mortality
	Tranexamic Acid (TA)		Combined Oral Contraceptives (COCP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tranexamic Acid (TA)		Combined Oral Contraceptives (COCP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Tranexamic Acid (TA)		Combined Oral Contraceptives (COCP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/10 (20%)		8/11 (72.7%)
General disorders
nausea/vomiting	1/10 (10%)	1	1/11 (9.1%)	1
abdominal pain	0/10 (0%)	0	1/11 (9.1%)	1
headache	0/10 (0%)	0	1/11 (9.1%)	1
weight gain	0/10 (0%)	0	1/11 (9.1%)	1
mood swings	0/10 (0%)	0	1/11 (9.1%)	1
depression and seizure	0/10 (0%)	0	1/11 (9.1%)	1
generalized rash	0/10 (0%)	0	1/11 (9.1%)	1
Lack of sleep	1/10 (10%)	1	0/11 (0%)	0
Reproductive system and breast disorders
breakthrough bleeding	1/10 (10%)	1	1/11 (9.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.