Trial Outcomes & Findings for The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension (NCT NCT03273387)

Last Updated: 2019-10-03

Results Overview

Right ventricular ejection fraction (RVEF %) assessed by Cardiac MRI at 3 months intervention minus with RVEF at baseline.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

26 participants

Primary outcome timeframe

Baseline and 3 months after intervention

Results posted on

2019-10-03

Participant Flow

Subjects were recruited from NCCHK PH outpatient clinic from September 2017 until November 2018

A total of 35 Patients were enrolled between September 2017 and November 2018 at NCCHK PAH outpatient clinic. A total of 26 patients were consent to underwent the trial and randomly assigned to receive trimetazidine or placebo with ratio 1:1.

Participant milestones

Participant milestones
Measure	Sugar Pill The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy. Placebo oral capsule: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.	Trimetazidine The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy. Trimetazidine: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.
Overall Study STARTED	13	13
Overall Study COMPLETED	10	10
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Sugar Pill The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy. Placebo oral capsule: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.	Trimetazidine The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy. Trimetazidine: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.
Overall Study Death	2	2
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

The Role of Trimetazidine on Right Ventricle Function in Pulmonary Arterial Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sugar Pill n=13 Participants The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy. Placebo oral capsule: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.	Trimetazidine n=13 Participants The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy. Trimetazidine: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.	Total n=26 Participants Total of all reporting groups
Age, Continuous	47 years STANDARD_DEVIATION 3.8 • n=5 Participants	48 years STANDARD_DEVIATION 1.5 • n=7 Participants	48 years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
onset of diagnosis to study	1170 days STANDARD_DEVIATION 387 • n=5 Participants	926 days STANDARD_DEVIATION 214 • n=7 Participants	1048 days STANDARD_DEVIATION 1093 • n=5 Participants
SF-36 Functional Capacity	61.15 units on a scale STANDARD_DEVIATION 4.77 • n=5 Participants	46.54 units on a scale STANDARD_DEVIATION 5.44 • n=7 Participants	53.84 units on a scale STANDARD_DEVIATION 19.56 • n=5 Participants
WHO Functional Class WHO functional class II	9 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants
WHO Functional Class WHO functional class III	4 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants
Glomerular Filtration Rate	96.6 ml/min/1.73 m^2 STANDARD_DEVIATION 7.9 • n=5 Participants	110.7 ml/min/1.73 m^2 STANDARD_DEVIATION 3.9 • n=7 Participants	106 ml/min/1.73 m^2 STANDARD_DEVIATION 15.6 • n=5 Participants
Body Mass Index	23.3 kg/m^2 STANDARD_DEVIATION 3.8 • n=5 Participants	21 kg/m^2 STANDARD_DEVIATION 0.8 • n=7 Participants	22.1 kg/m^2 STANDARD_DEVIATION 8.6 • n=5 Participants
Phosphodiesterase-5 inhibitor	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Prostacyclin analogue (beraprost)	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
beta blocker	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
ACE-inhibitor	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Angiotensin receptor II blocker	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Warfarin	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
spironolactone	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
furosemide	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
digoxin	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
mean Right atrial pressure	5.9 mmHg STANDARD_DEVIATION 1.4 • n=5 Participants	6 mmHg STANDARD_DEVIATION 1.2 • n=7 Participants	5.9 mmHg STANDARD_DEVIATION 3.9 • n=5 Participants
mean pulmonary arterial pressure	62 mmHg STANDARD_DEVIATION 5.9 • n=5 Participants	59 mmHg STANDARD_DEVIATION 3.6 • n=7 Participants	60 mmHg STANDARD_DEVIATION 11.2 • n=5 Participants
LV end diastolic pressure	7.2 mmHg STANDARD_DEVIATION 1.2 • n=5 Participants	7.8 mmHg STANDARD_DEVIATION 0.8 • n=7 Participants	7.4 mmHg STANDARD_DEVIATION 3.1 • n=5 Participants
RV end diastolic volume	258 ml STANDARD_DEVIATION 28 • n=5 Participants	260 ml STANDARD_DEVIATION 31 • n=7 Participants	259 ml STANDARD_DEVIATION 83 • n=5 Participants
RV end systolic volume	193 ml STANDARD_DEVIATION 20 • n=5 Participants	206 ml STANDARD_DEVIATION 25 • n=7 Participants	197 ml STANDARD_DEVIATION 67 • n=5 Participants
RV ejection fraction	24.5 % STANDARD_DEVIATION 2.8 • n=5 Participants	21.1 % STANDARD_DEVIATION 4.4 • n=7 Participants	22.4 % STANDARD_DEVIATION 10 • n=5 Participants
LV end diastolic volume	79 ml STANDARD_DEVIATION 6.3 • n=5 Participants	83 ml STANDARD_DEVIATION 5.3 • n=7 Participants	81 ml STANDARD_DEVIATION 18 • n=5 Participants
LV end systolic volume	29 ml STANDARD_DEVIATION 2.8 • n=5 Participants	33 ml STANDARD_DEVIATION 3.3 • n=7 Participants	31 ml STANDARD_DEVIATION 9.7 • n=5 Participants
LV ejection fraction	64 % STANDARD_DEVIATION 2.6 • n=5 Participants	59 % STANDARD_DEVIATION 2.4 • n=7 Participants	62 % STANDARD_DEVIATION 7.5 • n=5 Participants
Native T1 anteroseptal	993 ms STANDARD_DEVIATION 612 • n=5 Participants	1354 ms STANDARD_DEVIATION 441 • n=7 Participants	1164 ms STANDARD_DEVIATION 555 • n=5 Participants
Native T1 septal	1108 ms STANDARD_DEVIATION 512 • n=5 Participants	1110 ms STANDARD_DEVIATION 411 • n=7 Participants	1109 ms STANDARD_DEVIATION 454 • n=5 Participants
Native T1 inferoseptal	930 ms STANDARD_DEVIATION 418 • n=5 Participants	1474 ms STANDARD_DEVIATION 736 • n=7 Participants	1187 ms STANDARD_DEVIATION 637 • n=5 Participants
Native T1 Lateral	1090 ms STANDARD_DEVIATION 470 • n=5 Participants	1357 ms STANDARD_DEVIATION 473 • n=7 Participants	1216 ms STANDARD_DEVIATION 478 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 3 months after intervention

Population: A total 13 patients were assigned to each group equally. There were 6 patients who were not able to complete the study. A total of 2 patients from both group died due to RV failure. One patients from trimetazidine group withdrawn due to atypical angina and one patients from placebo group withdrawn due to claustrophobia.

Right ventricular ejection fraction (RVEF %) assessed by Cardiac MRI at 3 months intervention minus with RVEF at baseline.

Outcome measures

Outcome measures
Measure	Sugar Pill n=10 Participants The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy. Placebo oral capsule: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.	Trimetazidine n=10 Participants The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy. Trimetazidine: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.
Changes in Right Ventricular Ejection Fraction (RVEF %) After 3 Months Intervention	-2.8 percentage of ejected blood Standard Error 1.6	3.9 percentage of ejected blood Standard Error 1.5

SECONDARY outcome

Timeframe: Baseline and 3 months after intervention

Native T1 mapping (ms) assessed by Cardiac MRI at 3 months intervention minus with Native T1 at baseline.

Outcome measures

Outcome measures
Measure	Sugar Pill n=10 Participants The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy. Placebo oral capsule: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.	Trimetazidine n=10 Participants The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy. Trimetazidine: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.
Changes in Cardiac Fibrosis After 3 Months Intervention Native T1 anteroseptal	138 ms Standard Error 555	190 ms Standard Error 538
Changes in Cardiac Fibrosis After 3 Months Intervention Native T1 Septal	292 ms Standard Error 677	371 ms Standard Error 670
Changes in Cardiac Fibrosis After 3 Months Intervention Native T1 Inferoseptal	294 ms Standard Error 618	-123 ms Standard Error 645
Changes in Cardiac Fibrosis After 3 Months Intervention Native T1 Lateral	287 ms Standard Error 744	-194 ms Standard Error 487

SECONDARY outcome

Timeframe: Baseline and 3 months after intervention

Functional capacity assessed by SF-36 score after 3 month intervention minus with functional capacity at baseline. SF-36 functional capacity score scale 0 to 100 with better functional capacity along with higher score.

Outcome measures

Outcome measures
Measure	Sugar Pill n=10 Participants The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy. Placebo oral capsule: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.	Trimetazidine n=10 Participants The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy. Trimetazidine: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.
Changes in Functional Capacity After 3 Month Intervention	-17.73 score on a scale Standard Error 3.72	11.5 score on a scale Standard Error 5.27

Adverse Events

Sugar Pill

Serious events: 2 serious events

Other events: 1 other events

Deaths: 2 deaths

Trimetazidine

Serious events: 2 serious events

Other events: 2 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Sugar Pill n=13 participants at risk The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy. Placebo oral capsule: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.	Trimetazidine n=13 participants at risk The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy. Trimetazidine: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.
Cardiac disorders Cardiovascular mortality	15.4% 2/13 • Number of events 2 • three months for each intervention. safety population included all participants who received at least one dose of intervention.	15.4% 2/13 • Number of events 2 • three months for each intervention. safety population included all participants who received at least one dose of intervention.

Other adverse events

Other adverse events
Measure	Sugar Pill n=13 participants at risk The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy. Placebo oral capsule: The participant will received placebo oral capsule bid for 3 months on top of their regular PAH specific therapy.	Trimetazidine n=13 participants at risk The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy. Trimetazidine: The participant will received trimetazidine 35 mg bid for 3 months on top of their regular PAH specific therapy.
Nervous system disorders paresthesia	7.7% 1/13 • Number of events 1 • three months for each intervention. safety population included all participants who received at least one dose of intervention.	0.00% 0/13 • three months for each intervention. safety population included all participants who received at least one dose of intervention.
Gastrointestinal disorders nausea	0.00% 0/13 • three months for each intervention. safety population included all participants who received at least one dose of intervention.	7.7% 1/13 • Number of events 1 • three months for each intervention. safety population included all participants who received at least one dose of intervention.
Musculoskeletal and connective tissue disorders musculoskeletal angina	0.00% 0/13 • three months for each intervention. safety population included all participants who received at least one dose of intervention.	7.7% 1/13 • Number of events 1 • three months for each intervention. safety population included all participants who received at least one dose of intervention.

Additional Information

dr. Bambang WIdyantoro, FIHA, PhD

Department of Cardiology and Vascular Medicine, Universitas Indonesia

Phone: +628128164299

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place