Trial Outcomes & Findings for Simvastatin as a Treatment for Pulmonary Hypertension (NCT NCT00180713)

NCT ID: NCT00180713

Last Updated: 2019-08-21

Results Overview

As measured by cardiac magnetic resonance (the study is powered to detect an 8.5g difference in RV mass between the two treatments, based on reproducibility measurements of RV mass in healthy volunteers and patients)

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 42 participants
• Primary outcome timeframe: 6 months post study treatment
• Results posted on: 2019-08-21

Participant Flow

Participant milestones

Measure	Arm 1: Control Placebo tablet once daily Placebo: Placebo tablet once daily.	Arm 2: Experimental Simvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months. Simvastatin: Simvastatin 40mg od for 1 month, then 80mg od for 11 months
Overall Study STARTED	23	19
Overall Study COMPLETED	18	16
Overall Study NOT COMPLETED	5	3

Reasons for withdrawal

Measure	Arm 1: Control Placebo tablet once daily Placebo: Placebo tablet once daily.	Arm 2: Experimental Simvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months. Simvastatin: Simvastatin 40mg od for 1 month, then 80mg od for 11 months
Overall Study Withdrawal by Subject	2	0
Overall Study Adverse Event	3	3

Baseline Characteristics

Simvastatin as a Treatment for Pulmonary Hypertension

Baseline characteristics by cohort

Measure	Arm 1: Control n=23 Participants Placebo tablet once daily Placebo: Placebo tablet once daily.	Arm 2: Experimental n=19 Participants Simvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months. Simvastatin: Simvastatin 40mg od for 1 month, then 80mg od for 11 months	Total n=42 Participants Total of all reporting groups
Age, Continuous	49.1 years n=5 Participants	43.2 years n=7 Participants	46.2 years n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	2 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized White	21 participants n=5 Participants	11 participants n=7 Participants	32 participants n=5 Participants
Race/Ethnicity, Customized Black	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants	7 participants n=7 Participants	9 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months post study treatment

As measured by cardiac magnetic resonance (the study is powered to detect an 8.5g difference in RV mass between the two treatments, based on reproducibility measurements of RV mass in healthy volunteers and patients)

Outcome measures

Measure	Arm 1: Control n=23 Participants Placebo tablet once daily Placebo: Placebo tablet once daily.	Arm 2: Experimental n=19 Participants Simvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months. Simvastatin: Simvastatin 40mg od for 1 month, then 80mg od for 11 months
Change in Right Ventricular Mass From Baseline	3.9 grams Standard Deviation 13.9	-5.2 grams Standard Deviation 11.3

SECONDARY outcome

Timeframe: 6 months

Change in distance achieved in 6 minute walk test from baseline

Outcome measures

Measure	Arm 1: Control n=23 Participants Placebo tablet once daily Placebo: Placebo tablet once daily.	Arm 2: Experimental n=19 Participants Simvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months. Simvastatin: Simvastatin 40mg od for 1 month, then 80mg od for 11 months
Change in 6-minute Walk Distance	1 metres Standard Deviation 57	3.1 metres Standard Deviation 34.5

SECONDARY outcome

Timeframe: 6 months

Change in LV mass from baseline based on cardiac MRI

Outcome measures

Measure	Arm 1: Control n=23 Participants Placebo tablet once daily Placebo: Placebo tablet once daily.	Arm 2: Experimental n=19 Participants Simvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months. Simvastatin: Simvastatin 40mg od for 1 month, then 80mg od for 11 months
Change in LV Mass	-1.3 grams Standard Deviation 10.9	1.7 grams Standard Deviation 12.3

SECONDARY outcome

Timeframe: 6 months

Change in NT-proBNP levels compared to baseline

Outcome measures

Measure	Arm 1: Control n=23 Participants Placebo tablet once daily Placebo: Placebo tablet once daily.	Arm 2: Experimental n=19 Participants Simvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months. Simvastatin: Simvastatin 40mg od for 1 month, then 80mg od for 11 months
Circulating Levels of BNP	49 fmol/ml Standard Deviation 224	-75 fmol/ml Standard Deviation 167

SECONDARY outcome

Timeframe: 6 months

Change in quality of life score from baseline as measured by Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) scored from 1-25, with higher scores indicating worse quality of life, the investigator reported the score change.

Outcome measures

Measure	Arm 1: Control n=23 Participants Placebo tablet once daily Placebo: Placebo tablet once daily.	Arm 2: Experimental n=19 Participants Simvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months. Simvastatin: Simvastatin 40mg od for 1 month, then 80mg od for 11 months
Change in Quality of Life Score	0 change of score Standard Deviation 4.7	-1.6 change of score Standard Deviation 4

Adverse Events

Arm 1: Control

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm 2: Experimental

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arm 1: Control n=23 participants at risk Placebo tablet once daily Placebo: Placebo tablet once daily.	Arm 2: Experimental n=19 participants at risk Simvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months. Simvastatin: Simvastatin 40mg od for 1 month, then 80mg od for 11 months
Nervous system disorders Stroke	4.3% 1/23 • Number of events 1 • Adverse events were collected from date of consent until the final study visit after a year.	0.00% 0/19 • Adverse events were collected from date of consent until the final study visit after a year.

Other adverse events

Measure	Arm 1: Control n=23 participants at risk Placebo tablet once daily Placebo: Placebo tablet once daily.	Arm 2: Experimental n=19 participants at risk Simvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months. Simvastatin: Simvastatin 40mg od for 1 month, then 80mg od for 11 months
Investigations Elevated Creatinine Kinase	0.00% 0/23 • Adverse events were collected from date of consent until the final study visit after a year.	10.5% 2/19 • Number of events 2 • Adverse events were collected from date of consent until the final study visit after a year.

Additional Information

Professor Martin R Wilkins

Imperial College London

Phone: +44 (0)20 8383 2049

Email: m.wilkins@imperial.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee Standard terms of model non-commercial agreement for UK clinical research apply.
• Publication restrictions are in place

Restriction type: OTHER