Trial Outcomes & Findings for Atorvastatin (Lipitor) Therapy in Patients With Clinically Isolated Syndrome (CIS) at Risk for Multiple Sclerosis (NCT NCT00094172)
NCT ID: NCT00094172
Last Updated: 2017-04-28
Results Overview
The occurrence of ≥ T2 lesions\[1\] with or without gadolinium lesion (Gd+) enhancement\[2\] or clinical exacerbation\[3\] through 12 months. A higher score indicates more severe disease 1. A new T2 lesion is an abnormal, hyperintense white-matter area visible on T2 weighted images that were not present on the baseline scan 2. A Gd+ enhancement is defined as a contrast enhancement visible on a new T2 lesion 3. A clinical exacerbation is a new neurological symptom that lasts more than 48 hours in a participant who has been neurologically stable for 30 days following start of study medication
COMPLETED
PHASE2
82 participants
12 months post-randomization
2017-04-28
Participant Flow
Fourteen centers enrolled 83 participants and randomized 82 participants(one participant voluntarily withdrew prior to randomization) who had experienced clinically isolated syndrome and were at risk for developing Multiple Sclerosis (MS) (two or more lesions on Magnetic Resonance Image (MRI) scans) between February 14, 2005 and July 24, 2007.
At a screening visit, participants underwent procedures to establish that all inclusion criteria were met and none of the exclusion criteria were met. Participants then signed an informed consent form.
Participant milestones
| Measure |
Atorvastatin
Drug: Atorvastatin
|
Placebo
Non-Active Comparator
|
|---|---|---|
|
Overall Study
STARTED
|
50
|
32
|
|
Overall Study
COMPLETED
|
36
|
25
|
|
Overall Study
NOT COMPLETED
|
14
|
7
|
Reasons for withdrawal
| Measure |
Atorvastatin
Drug: Atorvastatin
|
Placebo
Non-Active Comparator
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
10
|
5
|
|
Overall Study
Primary endpoint met.
|
1
|
0
|
|
Overall Study
Started other MS therapy due to disease
|
1
|
0
|
Baseline Characteristics
Atorvastatin (Lipitor) Therapy in Patients With Clinically Isolated Syndrome (CIS) at Risk for Multiple Sclerosis
Baseline characteristics by cohort
| Measure |
Atorvastatin
n=50 Participants
Drug: Atorvastatin
|
Placebo
n=32 Participants
Non-Active Comparator
|
Total
n=82 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
33.6 years
STANDARD_DEVIATION 9.4 • n=5 Participants
|
33.9 years
STANDARD_DEVIATION 8.6 • n=7 Participants
|
33.7 years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
46 participants
n=5 Participants
|
29 participants
n=7 Participants
|
75 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Number of T2 Lesions at Baseline
|
21.6 Lesion Count
STANDARD_DEVIATION 17.6 • n=5 Participants
|
19.5 Lesion Count
STANDARD_DEVIATION 16.5 • n=7 Participants
|
20.8 Lesion Count
STANDARD_DEVIATION 17.1 • n=5 Participants
|
|
Number of Gd+ Lesions at Baseline
|
0.7 Lesion Count
STANDARD_DEVIATION 2.7 • n=5 Participants
|
0.2 Lesion Count
STANDARD_DEVIATION 0.5 • n=7 Participants
|
0.5 Lesion Count
STANDARD_DEVIATION 2.1 • n=5 Participants
|
PRIMARY outcome
Timeframe: 12 months post-randomizationPopulation: Intent-to-Treat
The occurrence of ≥ T2 lesions\[1\] with or without gadolinium lesion (Gd+) enhancement\[2\] or clinical exacerbation\[3\] through 12 months. A higher score indicates more severe disease 1. A new T2 lesion is an abnormal, hyperintense white-matter area visible on T2 weighted images that were not present on the baseline scan 2. A Gd+ enhancement is defined as a contrast enhancement visible on a new T2 lesion 3. A clinical exacerbation is a new neurological symptom that lasts more than 48 hours in a participant who has been neurologically stable for 30 days following start of study medication
Outcome measures
| Measure |
Atorvastatin
n=49 Participants
Drug: Atorvastatin
|
Placebo
n=32 Participants
Non-Active Comparator
|
|---|---|---|
|
The Occurrence of ≥ 3 New T2 Lesions With or Without Gd+ Enhancement or Clinical Exacerbation Through 12 Months.
|
26 Participants
|
18 Participants
|
SECONDARY outcome
Timeframe: 12 months post-randomizationPopulation: Intent-to-Treat
Number of participants diagnosed with Multiple Sclerosis (MS) according to the McDonald criteria\[1\] 1. The McDonald criteria uses dissemination in time and space\[2\] established by Magnetic Resonance Image (MRI) findings to provide a clinical diagnosis for MS 2. Dissemination in time is established by a new T2 or gadolinium-enhancing (Gd+) lesion found on a repeat MRI. The presence of any 3 of the following establishes dissemination in space: 1 Gd+ lesion or 9 T2 bright lesions if there is no enhancement; ≥1 infratentorial lesion; ≥1 juxtacortical lesion; ≥3 periventricular lesions
Outcome measures
| Measure |
Atorvastatin
n=49 Participants
Drug: Atorvastatin
|
Placebo
n=32 Participants
Non-Active Comparator
|
|---|---|---|
|
Proportion of Participants Who Are Diagnosed With Multiple Sclerosis According to the McDonald Criteria
|
29 Participants
|
24 Participants
|
SECONDARY outcome
Timeframe: 18 months post-randomizationPopulation: Intent-to-Treat
Number of participants diagnosed with Multiple Sclerosis (MS) according to the McDonald criteria\[1\] 1. The McDonald criteria uses dissemination in time and space\[2\] established by Magnetic Resonance Image (MRI) findings to provide a clinical diagnosis for MS 2. Dissemination in time is established by a new T2 or gadolinium-enhancing (Gd+) lesion found on a repeat MRI. The presence of any 3 of the following establishes dissemination in space: 1 Gd+ lesion or 9 T2 bright lesions if there is no enhancement; ≥1 infratentorial lesion; ≥1 juxtacortical lesion; ≥3 periventricular lesions
Outcome measures
| Measure |
Atorvastatin
n=49 Participants
Drug: Atorvastatin
|
Placebo
n=32 Participants
Non-Active Comparator
|
|---|---|---|
|
Proportion of Participants Diagnosed With Multiple Sclerosis According to the McDonald Criteria
|
37 Participants
|
24 Participants
|
Adverse Events
Atorvastatin
Placebo
Serious adverse events
| Measure |
Atorvastatin
n=51 participants at risk
Drug: Atorvastatin
|
Placebo
n=32 participants at risk
Non-Active Comparator
|
|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
2.0%
1/51 • Number of events 1 • 18 months
|
0.00%
0/32 • 18 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
2.0%
1/51 • Number of events 1 • 18 months
|
0.00%
0/32 • 18 months
|
|
Nervous system disorders
Convulsion
|
0.00%
0/51 • 18 months
|
3.1%
1/32 • Number of events 1 • 18 months
|
|
Reproductive system and breast disorders
Menorrhagia
|
2.0%
1/51 • Number of events 1 • 18 months
|
0.00%
0/32 • 18 months
|
Other adverse events
| Measure |
Atorvastatin
n=51 participants at risk
Drug: Atorvastatin
|
Placebo
n=32 participants at risk
Non-Active Comparator
|
|---|---|---|
|
Investigations
C-reactive protein increased
|
5.9%
3/51 • Number of events 3 • 18 months
|
6.2%
2/32 • Number of events 2 • 18 months
|
|
Investigations
Low density lipoprotein decreased
|
25.5%
13/51 • Number of events 18 • 18 months
|
3.1%
1/32 • Number of events 1 • 18 months
|
|
Investigations
Low density lipoprotein increased
|
5.9%
3/51 • Number of events 3 • 18 months
|
9.4%
3/32 • Number of events 3 • 18 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
19.6%
10/51 • Number of events 12 • 18 months
|
12.5%
4/32 • Number of events 5 • 18 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
15.7%
8/51 • Number of events 10 • 18 months
|
15.6%
5/32 • Number of events 9 • 18 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
7.8%
4/51 • Number of events 5 • 18 months
|
9.4%
3/32 • Number of events 3 • 18 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.8%
5/51 • Number of events 9 • 18 months
|
12.5%
4/32 • Number of events 4 • 18 months
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
11.8%
6/51 • Number of events 6 • 18 months
|
6.2%
2/32 • Number of events 2 • 18 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
15.7%
8/51 • Number of events 11 • 18 months
|
12.5%
4/32 • Number of events 6 • 18 months
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
7.8%
4/51 • Number of events 4 • 18 months
|
3.1%
1/32 • Number of events 2 • 18 months
|
|
Eye disorders
Eye pain
|
3.9%
2/51 • Number of events 6 • 18 months
|
12.5%
4/32 • Number of events 5 • 18 months
|
|
Eye disorders
Vision blurred
|
11.8%
6/51 • Number of events 9 • 18 months
|
15.6%
5/32 • Number of events 9 • 18 months
|
|
Gastrointestinal disorders
Nausea
|
27.5%
14/51 • Number of events 14 • 18 months
|
9.4%
3/32 • Number of events 4 • 18 months
|
|
Gastrointestinal disorders
Vomiting
|
5.9%
3/51 • Number of events 4 • 18 months
|
9.4%
3/32 • Number of events 3 • 18 months
|
|
General disorders
Asthenia
|
17.6%
9/51 • Number of events 10 • 18 months
|
15.6%
5/32 • Number of events 6 • 18 months
|
|
General disorders
Disease progression
|
45.1%
23/51 • Number of events 27 • 18 months
|
59.4%
19/32 • Number of events 22 • 18 months
|
|
General disorders
Fatigue
|
27.5%
14/51 • Number of events 16 • 18 months
|
25.0%
8/32 • Number of events 9 • 18 months
|
|
General disorders
Influenza like illness
|
13.7%
7/51 • Number of events 9 • 18 months
|
28.1%
9/32 • Number of events 14 • 18 months
|
|
Infections and infestations
Bronchitis
|
3.9%
2/51 • Number of events 2 • 18 months
|
9.4%
3/32 • Number of events 4 • 18 months
|
|
Infections and infestations
Nasopharyngitis
|
7.8%
4/51 • Number of events 5 • 18 months
|
12.5%
4/32 • Number of events 5 • 18 months
|
|
Infections and infestations
Sinusitis
|
7.8%
4/51 • Number of events 5 • 18 months
|
9.4%
3/32 • Number of events 3 • 18 months
|
|
Infections and infestations
Upper respiratory tract infection
|
15.7%
8/51 • Number of events 16 • 18 months
|
25.0%
8/32 • Number of events 11 • 18 months
|
|
Infections and infestations
Urinary tract infection
|
3.9%
2/51 • Number of events 3 • 18 months
|
12.5%
4/32 • Number of events 7 • 18 months
|
|
Investigations
Alanine aminotransferase increased
|
17.6%
9/51 • Number of events 18 • 18 months
|
3.1%
1/32 • Number of events 1 • 18 months
|
|
Investigations
Aspartate aminotransferase increased
|
15.7%
8/51 • Number of events 14 • 18 months
|
3.1%
1/32 • Number of events 1 • 18 months
|
|
Investigations
Blood creatine phosphokinase increased
|
7.8%
4/51 • Number of events 4 • 18 months
|
6.2%
2/32 • Number of events 3 • 18 months
|
|
Nervous system disorders
Dizziness
|
13.7%
7/51 • Number of events 8 • 18 months
|
15.6%
5/32 • Number of events 6 • 18 months
|
|
Nervous system disorders
Headache
|
23.5%
12/51 • Number of events 17 • 18 months
|
21.9%
7/32 • Number of events 10 • 18 months
|
|
Nervous system disorders
Hypoaesthesia
|
39.2%
20/51 • Number of events 41 • 18 months
|
50.0%
16/32 • Number of events 26 • 18 months
|
|
Nervous system disorders
Migraine
|
9.8%
5/51 • Number of events 5 • 18 months
|
3.1%
1/32 • Number of events 1 • 18 months
|
|
Nervous system disorders
Multiple sclerosis
|
5.9%
3/51 • Number of events 4 • 18 months
|
9.4%
3/32 • Number of events 3 • 18 months
|
|
Nervous system disorders
Paraesthesia
|
25.5%
13/51 • Number of events 15 • 18 months
|
25.0%
8/32 • Number of events 14 • 18 months
|
|
Psychiatric disorders
Anxiety
|
9.8%
5/51 • Number of events 6 • 18 months
|
3.1%
1/32 • Number of events 1 • 18 months
|
|
Psychiatric disorders
Depression
|
15.7%
8/51 • Number of events 8 • 18 months
|
31.2%
10/32 • Number of events 10 • 18 months
|
|
Psychiatric disorders
Insomnia
|
21.6%
11/51 • Number of events 11 • 18 months
|
18.8%
6/32 • Number of events 6 • 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.0%
1/51 • Number of events 1 • 18 months
|
15.6%
5/32 • Number of events 6 • 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
9.8%
5/51 • Number of events 5 • 18 months
|
6.2%
2/32 • Number of events 3 • 18 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.8%
4/51 • Number of events 4 • 18 months
|
9.4%
3/32 • Number of events 4 • 18 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place