Trial Outcomes & Findings for Atorvastatin Treatment of Cavernous Angiomas With Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial (NCT NCT02603328)

Last Updated: 2025-08-22

Results Overview

QSM change score is the Percentage Change in mean lesional iron deposition per year (QSM score) according to assigned treatment (modified intention-to-treat cohort), presented as a mean value across all participants from baseline to year 1 and year 1 to year 2 follow-up MRIs. Quantitative susceptibility mapping (QSM) is a noninvasive MRI technique that assesses iron content by quantifying the magnetic susceptibility of local tissues. A higher QSM value corresponds to a larger amount of iron in the lesion, which means more blood is present in the lesion.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

80 participants

Primary outcome timeframe

2 years of follow-up

Results posted on

2025-08-22

Participant Flow

80 participants were randomized and followed for 2 years and all results are provided only for these participants.

Participant milestones

Participant milestones
Measure	Treatment 80mg Atorvastatin 80mg OD (optimal dose). Treatment dose will be de-escalated to 40mg based on reported adverse events. Atorvastatin: 40-80 mg OD	Placebo Identically looking capsules containing no active ingredient Placebo: inactive
Overall Study STARTED	41	39
Overall Study Completed Year 1	34	36
Overall Study Lowered to 40mg Dose in Year 1	1	0
Overall Study Completed Year 2	31	31
Overall Study Lowered to 40mg Dose in Year 2	0	0
Overall Study COMPLETED	31	31
Overall Study NOT COMPLETED	10	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Atorvastatin Treatment of Cavernous Angiomas With Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment n=41 Participants Atorvastatin 80mg OD (optimal dose). Treatment dose will be de-escalated to 40mg based on reported adverse events. Atorvastatin: 40-80 mg OD	Placebo n=39 Participants Identically looking capsules containing no active ingredient Placebo: inactive	Total n=80 Participants Total of all reporting groups
Age, Continuous	39 Years n=5 Participants	41 Years n=7 Participants	41 Years n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	25 Participants n=7 Participants	51 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	34 Participants n=5 Participants	31 Participants n=7 Participants	65 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 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	1 Participants n=5 Participants	1 Participants n=7 Participants	2 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	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	32 Participants n=5 Participants	31 Participants n=7 Participants	63 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Familial cavernous malformation syndrome	18 Participants n=5 Participants	11 Participants n=7 Participants	29 Participants n=5 Participants
MRI characteristics - number of lesions Number of lesions on susceptibility weighted imaging in familial cases	1 Lesions n=5 Participants	1 Lesions n=7 Participants	1 Lesions n=5 Participants
MRI characteristics - number of lesions Number of lesions on T2 ≥4mm in familial cases	1 Lesions n=5 Participants	1 Lesions n=7 Participants	1 Lesions n=5 Participants
Location of index CCM lesion with symptomatic hemorrhage Brainstem	23 participants n=5 Participants	21 participants n=7 Participants	44 participants n=5 Participants
Location of index CCM lesion with symptomatic hemorrhage Cerebellum	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Location of index CCM lesion with symptomatic hemorrhage Frontal Lobe	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Location of index CCM lesion with symptomatic hemorrhage Occipital Lobe	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Location of index CCM lesion with symptomatic hemorrhage Parietal Lobe	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Location of index CCM lesion with symptomatic hemorrhage Temporal Lobe	2 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants
Location of index CCM lesion with symptomatic hemorrhage Thalamus	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Location of index CCM lesion with symptomatic hemorrhage Other location	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Time from most recent symptomatic hemorrhage to enrollment, days	103 Days n=5 Participants	104 Days n=7 Participants	104 Days n=5 Participants
Number of symptomatic hemorrhages before enrollment	1 Number of symptomatic hemorrhages n=5 Participants	1 Number of symptomatic hemorrhages n=7 Participants	1 Number of symptomatic hemorrhages n=5 Participants
Modified Rankin Scale score 0	6 participants n=5 Participants	8 participants n=7 Participants	14 participants n=5 Participants
Modified Rankin Scale score 1	18 participants n=5 Participants	25 participants n=7 Participants	43 participants n=5 Participants
Modified Rankin Scale score 2-3	17 participants n=5 Participants	6 participants n=7 Participants	23 participants n=5 Participants
Modified Rankin Scale score 4	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Modified Rankin Scale score 5-6	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
European quality of life index Visual Analog Scale	74.59 units on a scale STANDARD_DEVIATION 16.29 • n=5 Participants	78.28 units on a scale STANDARD_DEVIATION 12.67 • n=7 Participants	76.4 units on a scale STANDARD_DEVIATION 14.7 • n=5 Participants
MRI characteristics - size of lesion on T2, mm	14.70 Size on T2, mm n=5 Participants	16 Size on T2, mm n=7 Participants	14.80 Size on T2, mm n=5 Participants

PRIMARY outcome

Timeframe: 2 years of follow-up

Outcome measures

Outcome measures
Measure	Treatment n=33 Participants Atorvastatin 80mg OD (optimal dose). Treatment dose will be de-escalated to 40mg based on reported adverse events. Atorvastatin: 40-80 mg OD	Placebo n=31 Participants Identically looking capsules containing no active ingredient Placebo: inactive
Percent Change in Mean Lesional QSM (QSM Change Score) QSM change score by assigned treatment; year 1 minus baseline	7.35 absolute value of percent change Standard Error 9.77	0.24 absolute value of percent change Standard Error 10.08
Percent Change in Mean Lesional QSM (QSM Change Score) QSM change score by assigned treatment; year 2 minus year 1	15.18 absolute value of percent change Standard Error 10.80	26.80 absolute value of percent change Standard Error 11.22

SECONDARY outcome

Timeframe: 2 years of follow-up

DCEQP change score is the absolute value of the Percent Change in DCEQP value of the index lesion, presented as a mean value across all participants from baseline to year 1 and year 1 to year 2 follow-up MRIs DCEQP measures vascular permeability and perfusion, in this case as measured in the index lesion. A higher DCEQP value reflects higher permeability in the lesion.

Outcome measures

Outcome measures
Measure	Treatment n=33 Participants Atorvastatin 80mg OD (optimal dose). Treatment dose will be de-escalated to 40mg based on reported adverse events. Atorvastatin: 40-80 mg OD	Placebo n=31 Participants Identically looking capsules containing no active ingredient Placebo: inactive
Percent Change in Dynamic Contrast-enhanced Quantitative Perfusion (DCEQP) Value (Vascular Permeability) in Index Lesion (Lesional DCEQP Change Score) Mean lesional DCEQP percent change by assigned treatment; year one minus baseline	103.40 percent change Standard Error 40.64	35.69 percent change Standard Error 50.59
Percent Change in Dynamic Contrast-enhanced Quantitative Perfusion (DCEQP) Value (Vascular Permeability) in Index Lesion (Lesional DCEQP Change Score) Mean lesional DCEQP percent change by assigned treatment; year two minus year one	124.52 percent change Standard Error 85.15	124.82 percent change Standard Error 88.92

SECONDARY outcome

Timeframe: 1 year of follow-up

Compare the changes in modified Rankin Score between atorvastatin and placebo groups at the year 1 follow-up visit. The mRS is a simple global measure of functional disability. Scores range from 0 (no symptoms) to 6 (death). An mRS score of 0 to 1 is considered a minimal clinical disability, and 0 to 2 is independent.

Outcome measures

Outcome measures
Measure	Treatment n=35 Participants Atorvastatin 80mg OD (optimal dose). Treatment dose will be de-escalated to 40mg based on reported adverse events. Atorvastatin: 40-80 mg OD	Placebo n=36 Participants Identically looking capsules containing no active ingredient Placebo: inactive
Compare the Changes in Modified Rankin Score Between Atorvastatin and Placebo Groups at the Year 1 Follow-up Visit mRS 5-6	0 Participants	0 Participants
Compare the Changes in Modified Rankin Score Between Atorvastatin and Placebo Groups at the Year 1 Follow-up Visit mRS 0	2 Participants	8 Participants
Compare the Changes in Modified Rankin Score Between Atorvastatin and Placebo Groups at the Year 1 Follow-up Visit mRS 1	25 Participants	20 Participants
Compare the Changes in Modified Rankin Score Between Atorvastatin and Placebo Groups at the Year 1 Follow-up Visit mRS 2-3	8 Participants	8 Participants
Compare the Changes in Modified Rankin Score Between Atorvastatin and Placebo Groups at the Year 1 Follow-up Visit mRS 4	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 1 year of follow-up (from year 1 to year 2)

Compare the changes in modified Rankin Score between atorvastatin and placebo groups at the year 2 follow-up visit (change between mRS score at year 1 follow up visit and year 2 follow up visit). The mRS is a simple global measure of functional disability. Scores range from 0 (no symptoms) to 6 (death). An mRS score of 0 to 1 is considered a minimal clinical disability, and 0 to 2 is independent.

Outcome measures

Outcome measures
Measure	Treatment n=31 Participants Atorvastatin 80mg OD (optimal dose). Treatment dose will be de-escalated to 40mg based on reported adverse events. Atorvastatin: 40-80 mg OD	Placebo n=31 Participants Identically looking capsules containing no active ingredient Placebo: inactive
Compare the Changes in Modified Rankin Score Between Atorvastatin and Placebo Groups at the Year 2 Follow-up Visit. mRS 0	6 Participants	12 Participants
Compare the Changes in Modified Rankin Score Between Atorvastatin and Placebo Groups at the Year 2 Follow-up Visit. mRS 1	17 Participants	12 Participants
Compare the Changes in Modified Rankin Score Between Atorvastatin and Placebo Groups at the Year 2 Follow-up Visit. mRS 2-3	7 Participants	7 Participants
Compare the Changes in Modified Rankin Score Between Atorvastatin and Placebo Groups at the Year 2 Follow-up Visit. mRS 4	1 Participants	0 Participants
Compare the Changes in Modified Rankin Score Between Atorvastatin and Placebo Groups at the Year 2 Follow-up Visit. mRS 5-6	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 1 year of follow up

Mean score of European Quality of Life Visual Analogue Scale (EQ-VAS) at the year 1 follow-up visit The EQ-VAS is a vertical visual analogue scale that takes values between 100 (best imaginable health) and 0 (worst imaginable health), on which patients provide a global assessment of their health.

Outcome measures

Outcome measures
Measure	Treatment n=35 Participants Atorvastatin 80mg OD (optimal dose). Treatment dose will be de-escalated to 40mg based on reported adverse events. Atorvastatin: 40-80 mg OD	Placebo n=36 Participants Identically looking capsules containing no active ingredient Placebo: inactive
Mean Score of European Quality of Life Visual Analogue Scale (EQ-VAS) at the Year 1 Follow-up Visit.	78.3 score on a scale Standard Deviation 17.5	78.1 score on a scale Standard Deviation 17.1

SECONDARY outcome

Timeframe: 1 year of follow up (from year 1 to year 2)

Mean score of European Quality of Life Visual Analogue Scale (EQ-VAS) at the year 2 follow-up visit The EQ-VAS is a vertical visual analogue scale that takes values between 100 (best imaginable health) and 0 (worst imaginable health), on which patients provide a global assessment of their health.

Outcome measures

Outcome measures
Measure	Treatment n=31 Participants Atorvastatin 80mg OD (optimal dose). Treatment dose will be de-escalated to 40mg based on reported adverse events. Atorvastatin: 40-80 mg OD	Placebo n=31 Participants Identically looking capsules containing no active ingredient Placebo: inactive
Mean Score of European Quality of Life Visual Analogue Scale (EQ-VAS) at the Year 2 Follow-up Visit	80.1 score on a scale Standard Deviation 16.0	80.5 score on a scale Standard Deviation 12.0

SECONDARY outcome

Timeframe: 2 years of follow-up

Compare number of subjects with 90% or greater protocol compliance throughout the 2 year follow-up period

Outcome measures

Outcome measures
Measure	Treatment n=33 Participants Atorvastatin 80mg OD (optimal dose). Treatment dose will be de-escalated to 40mg based on reported adverse events. Atorvastatin: 40-80 mg OD	Placebo n=31 Participants Identically looking capsules containing no active ingredient Placebo: inactive
Compare Rate of Drug Compliance in Atorvastatin vs Placebo Group	33 Participants	31 Participants

SECONDARY outcome

Timeframe: 1 year of follow-up

Compare the mean percent change in peripheral blood leukocyte ROCK activity between atorvastatin and placebo groups from baseline to year 1

Outcome measures

Outcome measures
Measure	Treatment n=33 Participants Atorvastatin 80mg OD (optimal dose). Treatment dose will be de-escalated to 40mg based on reported adverse events. Atorvastatin: 40-80 mg OD	Placebo n=31 Participants Identically looking capsules containing no active ingredient Placebo: inactive
Mean Percent Change in Rho-associated Protein Kinase (ROCK) Activity in Peripheral Blood Leukocytes From Baseline to Year 1	32.68 percent change Standard Deviation 75.72	22.73 percent change Standard Deviation 80.21

SECONDARY outcome

Timeframe: 2 year follow-up

Compare the mean percent change in peripheral blood leukocyte ROCK activity between atorvastatin and placebo groups from baseline to year 2

Outcome measures

Outcome measures
Measure	Treatment n=33 Participants Atorvastatin 80mg OD (optimal dose). Treatment dose will be de-escalated to 40mg based on reported adverse events. Atorvastatin: 40-80 mg OD	Placebo n=31 Participants Identically looking capsules containing no active ingredient Placebo: inactive
Mean Percent Change in Rho-associated Protein Kinase (ROCK) Activity in Peripheral Blood Leukocytes From Baseline to Year 2	68.17 percent change Standard Deviation 101.2	55.62 percent change Standard Deviation 95.22

Adverse Events

Atorvastatin 80mg

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

Atorvastatin 40mg

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Atorvastatin 80mg n=40 participants at risk Atorvastatin 80mg OD (optimal dose). Treatment dose will be de-escalated to 40mg based on reported adverse events. Atorvastatin: 80 mg OD	Atorvastatin 40mg n=1 participants at risk Atorvastatin 40mg. Treatment dose was de-escalated to 40mg based on reported adverse events. Atorvastatin: 40 mg	Placebo n=39 participants at risk Identically looking capsules containing no active ingredient Placebo: inactive
Musculoskeletal and connective tissue disorders Elevated creatine kinase (CK)	2.5% 1/40 • Number of events 1 • 2 years Subjects were contacted every 3 months to inquire about adverse events, initially by phone and later by protocol mandated self-reporting via the study phone app.	0.00% 0/1 • 2 years Subjects were contacted every 3 months to inquire about adverse events, initially by phone and later by protocol mandated self-reporting via the study phone app.	0.00% 0/39 • 2 years Subjects were contacted every 3 months to inquire about adverse events, initially by phone and later by protocol mandated self-reporting via the study phone app.
Injury, poisoning and procedural complications Fall	0.00% 0/40 • 2 years Subjects were contacted every 3 months to inquire about adverse events, initially by phone and later by protocol mandated self-reporting via the study phone app.	100.0% 1/1 • Number of events 2 • 2 years Subjects were contacted every 3 months to inquire about adverse events, initially by phone and later by protocol mandated self-reporting via the study phone app.	0.00% 0/39 • 2 years Subjects were contacted every 3 months to inquire about adverse events, initially by phone and later by protocol mandated self-reporting via the study phone app.

Other adverse events

Additional Information

Agnieszka Stadnik

University of Chicago, Medicine and Biological Sciences Division

Phone: 773-702-8996

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place