Trial Outcomes & Findings for Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension (NCT NCT03528902)

Last Updated: 2024-12-05

Results Overview

Transthoracic echocardiograms (ECHOs) will be performed to measure the TAPSE value prior to Intervention at Week 0, as well as at the end of the study intervention (Week 24). The primary outcome measure will be the change in TAPSE, determined by echocardiogram, from Week 0 to Week 24. About TAPSE: Tricuspid annular plane systolic excursion (TAPSE) is a parameter of global right ventricular function which describes apex-to-base shortening of the ventricle. It is obtained by transthoracic echocardiogram, which can be performed on a resting subject without sedation in the outpatient setting. TAPSE correlates closely with the right ventricular ejection fraction, and has been determined to be both highly specific and easy to measure.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

24 weeks

Results posted on

2024-12-05

Participant Flow

Recruitment occurred between 1/08/2018-12/28/2022

Participant milestones

Participant milestones
Measure	Tamoxifen 20 mg po TID for 24 weeks Tamoxifen: Tamoxifen 20 mg po daily for 24 weeks.	Placebo Placebo arm Placebo Oral Tablet: Placebo daily for 24 weeks.
Overall Study STARTED	9	9
Overall Study COMPLETED	8	9
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Tamoxifen 20 mg po TID for 24 weeks Tamoxifen: Tamoxifen 20 mg po daily for 24 weeks.	Placebo Placebo arm Placebo Oral Tablet: Placebo daily for 24 weeks.
Overall Study Adverse Event	1	0

Baseline Characteristics

Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tamoxifen n=9 Participants 20 mg po TID for 24 weeks Tamoxifen: Tamoxifen 20 mg po daily for 24 weeks.	Placebo n=9 Participants Placebo arm Placebo Oral Tablet: Placebo daily for 24 weeks.	Total n=18 Participants Total of all reporting groups
Age, Continuous	45.8 years STANDARD_DEVIATION 12.4 • n=5 Participants	51 years STANDARD_DEVIATION 10.5 • n=7 Participants	48.4 years STANDARD_DEVIATION 11.4 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	9 participants n=5 Participants	9 participants n=7 Participants	18 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Outcome measures

Outcome measures
Measure	Tamoxifen n=8 Participants 20 mg po TID for 24 weeks Tamoxifen: Tamoxifen 20 mg po daily for 24 weeks.	Placebo n=8 Participants Placebo arm Placebo Oral Tablet: Placebo daily for 24 weeks.
Transthoracic Echocardiogram (ECHO)-Based Change in the Tricuspid Annular Plane Systolic Excursion (TAPSE) Measurement Baseline	2.244 mm Standard Deviation 0.194	2.244 mm Standard Deviation 0.274
Transthoracic Echocardiogram (ECHO)-Based Change in the Tricuspid Annular Plane Systolic Excursion (TAPSE) Measurement Week 24	2.300 mm Standard Deviation 0.220	2.212 mm Standard Deviation 0.352

SECONDARY outcome

Timeframe: 24 weeks

Change in 6MWTD from Week 0 to Week 24. The 6-minute walk test distance (6MWTD) is a widely accepted measure of exercise capacity and functional status. The 6MWTD is a clinical and research test obtained in a standardized manner according to American Thoracic Society (ATS) Guidelines. Briefly, the 6MWT is a sub-maximal exercise test on flat ground that is used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity over time.

Outcome measures

Outcome measures
Measure	Tamoxifen n=8 Participants 20 mg po TID for 24 weeks Tamoxifen: Tamoxifen 20 mg po daily for 24 weeks.	Placebo n=8 Participants Placebo arm Placebo Oral Tablet: Placebo daily for 24 weeks.
Six Minute Walk Test Distance (6MWTD) Baseline	375.3 Meters Standard Deviation 78.4	415.2 Meters Standard Deviation 87.5
Six Minute Walk Test Distance (6MWTD) Week 24	377.9 Meters Standard Deviation 84.5	405.5 Meters Standard Deviation 156.4

SECONDARY outcome

Timeframe: 24 weeks

Change in score from Week 0 to Week 24. Specifically, Quality of life will be assessed using two different accepted questionnaires for pulmonary hypertension patients, the SF36 questionnaires. These will be administered at baseline and 12 and 24 weeks. Note that all items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.

Outcome measures

Outcome measures
Measure	Tamoxifen n=9 Participants 20 mg po TID for 24 weeks Tamoxifen: Tamoxifen 20 mg po daily for 24 weeks.	Placebo n=9 Participants Placebo arm Placebo Oral Tablet: Placebo daily for 24 weeks.
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. energy_fatigue (Baseline)	37.5 score on a scale Interval 18.8 to 62.5	62.5 score on a scale Interval 50.0 to 75.0
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. well_being (Baseline)	75 score on a scale Interval 60.0 to 90.0	90 score on a scale Interval 85.0 to 100.0
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. well_being (Week 24)	77.5 score on a scale Interval 68.8 to 92.5	90 score on a scale Interval 65.0 to 90.0
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. physical_functioning (Baseline)	55 score on a scale Interval 35.0 to 55.0	65 score on a scale Interval 45.0 to 85.0
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. physical_health(Baseline)	31.2 score on a scale Interval 12.5 to 62.5	81.2 score on a scale Interval 50.0 to 93.8
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. emotional_probs (Baseline)	66.67 score on a scale Interval 25.0 to 91.67	100 score on a scale Interval 91.67 to 100.0
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. social_function (Baseline)	62.5 score on a scale Interval 50.0 to 87.5	100 score on a scale Interval 87.5 to 100.0
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. pain (Baseline)	67.5 score on a scale Interval 45.0 to 90.0	67.5 score on a scale Interval 60.0 to 90.0
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. gen_health(Baseline)	40 score on a scale Interval 35.0 to 45.0	50 score on a scale Interval 35.0 to 65.0
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. physical_functioning (Week 24)	55 score on a scale Interval 38.8 to 72.5	65 score on a scale Interval 55.0 to 78.6
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. physical_health (week 24)	40.6 score on a scale Interval 28.1 to 50.0	93.8 score on a scale Interval 50.0 to 100.0
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. emotional_probs (Week 24)	58.3 score on a scale Interval 50.0 to 100.0	100 score on a scale Interval 100.0 to 100.0
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. energy_fatigue (Week 24)	59.4 score on a scale Interval 45.3 to 81.2	62.5 score on a scale Interval 50.0 to 81.2
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. social_function (Week 24)	81.2 score on a scale Interval 50.0 to 100.0	100 score on a scale Interval 62.5 to 100.0
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. pain (Week 24)	67.5 score on a scale Interval 51.9 to 77.5	77.5 score on a scale Interval 45.0 to 90.0
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. gen_health (Week 24)	37.5 score on a scale Interval 28.8 to 56.2	40 score on a scale Interval 35.0 to 70.0

SECONDARY outcome

Timeframe: 24 weeks

This will be administered at baseline and 12 and 24 weeks. Change in score from Week 0 to Week 24 will be reported. emPHasis-10 scores range from 0 to 50, higher scores indicate worse quality of life

Outcome measures

Outcome measures
Measure	Tamoxifen n=8 Participants 20 mg po TID for 24 weeks Tamoxifen: Tamoxifen 20 mg po daily for 24 weeks.	Placebo n=9 Participants Placebo arm Placebo Oral Tablet: Placebo daily for 24 weeks.
Quality of Life Will be Assessed Using emPHasis-10 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. Week 24	23.5 units on a scale Standard Deviation 12.7	15.9 units on a scale Standard Deviation 13.7
Quality of Life Will be Assessed Using emPHasis-10 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks. Baseline	25.7 units on a scale Standard Deviation 13.9	14.3 units on a scale Standard Deviation 11.7

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 weeks

Change in Plasma BNP levels will be assessed from Week 0 to Week 24 during the study. These measurements are made from the plasma, and will require a blood draw from the research participant.

Outcome measures

Outcome measures
Measure	Tamoxifen n=8 Participants 20 mg po TID for 24 weeks Tamoxifen: Tamoxifen 20 mg po daily for 24 weeks.	Placebo n=8 Participants Placebo arm Placebo Oral Tablet: Placebo daily for 24 weeks.
Plasma BNP Baseline	30.4 pg/mL Standard Deviation 31.3	79.1 pg/mL Standard Deviation 110.5
Plasma BNP Week 24	101.3 pg/mL Standard Deviation 150.9	76.2 pg/mL Standard Deviation 77.1

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 weeks

Population: HgbA1c was not assessed due to assay issues.

Change in hemoglobin A1c (HgbA1c) levels will be assessed from Week 0 to Week 24 during the study. These measurements are made from the plasma, and will require a blood draw from the research participant.

Outcome measures

Outcome data not reported

Adverse Events

Tamoxifen

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tamoxifen n=9 participants at risk 20 mg po TID for 24 weeks Tamoxifen: Tamoxifen 20 mg po daily for 24 weeks.	Placebo n=9 participants at risk Placebo arm Placebo Oral Tablet: Placebo daily for 24 weeks.
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/9 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.	11.1% 1/9 • Number of events 1 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.
Infections and infestations Bacteremia	0.00% 0/9 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.	11.1% 1/9 • Number of events 1 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.
Cardiac disorders Arrhythmia	0.00% 0/9 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.	11.1% 1/9 • Number of events 1 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.

Other adverse events

Other adverse events
Measure	Tamoxifen n=9 participants at risk 20 mg po TID for 24 weeks Tamoxifen: Tamoxifen 20 mg po daily for 24 weeks.	Placebo n=9 participants at risk Placebo arm Placebo Oral Tablet: Placebo daily for 24 weeks.
General disorders Hot Flashes	33.3% 3/9 • Number of events 3 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.	11.1% 1/9 • Number of events 1 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.
General disorders Night Sweats	11.1% 1/9 • Number of events 1 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.	22.2% 2/9 • Number of events 4 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.
Psychiatric disorders Mood Alterations	11.1% 1/9 • Number of events 1 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.	22.2% 2/9 • Number of events 2 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.
General disorders Nonspecific pain	11.1% 1/9 • Number of events 1 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.	0.00% 0/9 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.
General disorders Alteration in smell	0.00% 0/9 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.	11.1% 1/9 • Number of events 1 • AEs were monitored throughout the duration of enrollment but were specifically reviewed with participants at weeks 3, 6, 9, 12, 15, 18, 21 and 24.

Additional Information

Research Programs Manager

Vanderbilt University Medical Center

Phone: 615-322-4703

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place