Trial Outcomes & Findings for Idiopathic Intracranial Hypertension Treatment Trial (NCT NCT01003639)
NCT ID: NCT01003639
Last Updated: 2018-12-12
Results Overview
Treatment Effects on the Primary Outcome Variable, Mean change From Baseline to Month 6 in Perimetric Mean Deviation (PMD) in the Study Eye. Perimetric mean deviation is a measure of global visual field loss (mean deviation from age-corrected normal values), with a range of 2 to -32 dB; larger negative values indicate greater vision loss.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
165 participants
Primary outcome timeframe
base line and 6 months
Results posted on
2018-12-12
Participant Flow
Participants were enrolled at 38 academic and private practice sites in North America from March 2010 to November 2012,with follow-up ending in June 2013.
Randomization was stratified by site and included blocking to ensure balance among the treatment groups within a site after every 4 participants had been enrolled at that site.
Participant milestones
| Measure |
Acetazolamide
Acetazolamide given in escalating doses
Acetazolamide: Subjects will begin with four 250 mg tablets daily.
|
Sugar Pill
Given in escalating "dose" (number of pill)
Placebo: Subjects will begin with four tablets daily.
|
|---|---|---|
|
Overall Study
STARTED
|
86
|
79
|
|
Overall Study
COMPLETED
|
69
|
57
|
|
Overall Study
NOT COMPLETED
|
17
|
22
|
Reasons for withdrawal
| Measure |
Acetazolamide
Acetazolamide given in escalating doses
Acetazolamide: Subjects will begin with four 250 mg tablets daily.
|
Sugar Pill
Given in escalating "dose" (number of pill)
Placebo: Subjects will begin with four tablets daily.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
6
|
9
|
|
Overall Study
Withdrawal by Subject
|
9
|
5
|
|
Overall Study
Lack of Efficacy
|
1
|
6
|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Physician Decision
|
1
|
0
|
Baseline Characteristics
Idiopathic Intracranial Hypertension Treatment Trial
Baseline characteristics by cohort
| Measure |
Acetazolamide
n=86 Participants
Acetazolamide given in escalating doses
Acetazolamide: Subjects will begin with four 250 mg tablets daily.
|
Sugar Pill
n=79 Participants
Given in escalating "dose" (number of pill)
Placebo: Subjects will begin with four tablets daily.
|
Total
n=165 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
28.2 years
STANDARD_DEVIATION 6.9 • n=5 Participants
|
30.0 years
STANDARD_DEVIATION 8.0 • n=7 Participants
|
29.0 years
STANDARD_DEVIATION 7.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
84 Participants
n=5 Participants
|
77 Participants
n=7 Participants
|
161 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 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
|
25 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
54 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
108 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Weight
|
108.1 kg
STANDARD_DEVIATION 25.6 • n=5 Participants
|
107.3 kg
STANDARD_DEVIATION 24.5 • n=7 Participants
|
107.7 kg
STANDARD_DEVIATION 25.0 • n=5 Participants
|
|
Body mass index
|
40.0 Kg/m^2
STANDARD_DEVIATION 8.5 • n=5 Participants
|
39.9 Kg/m^2
STANDARD_DEVIATION 8.1 • n=7 Participants
|
39.9 Kg/m^2
STANDARD_DEVIATION 8.3 • n=5 Participants
|
|
Weight change in the past 6 mo
|
10.7 kg
STANDARD_DEVIATION 16.7 • n=5 Participants
|
8.8 kg
STANDARD_DEVIATION 16.9 • n=7 Participants
|
9.8 kg
STANDARD_DEVIATION 16.7 • n=5 Participants
|
|
Transient visual obscurations
yes
|
55 participants
n=5 Participants
|
57 participants
n=7 Participants
|
112 participants
n=5 Participants
|
|
Transient visual obscurations
No
|
31 participants
n=5 Participants
|
22 participants
n=7 Participants
|
53 participants
n=5 Participants
|
|
Diplopia
Yes
|
20 participants
n=5 Participants
|
16 participants
n=7 Participants
|
36 participants
n=5 Participants
|
|
Diplopia
No
|
66 participants
n=5 Participants
|
63 participants
n=7 Participants
|
129 participants
n=5 Participants
|
|
Constant visual loss
Yes
|
25 participants
n=5 Participants
|
28 participants
n=7 Participants
|
53 participants
n=5 Participants
|
|
Constant visual loss
No
|
61 participants
n=5 Participants
|
51 participants
n=7 Participants
|
112 participants
n=5 Participants
|
|
Photophobia
Yes
|
42 participants
n=5 Participants
|
37 participants
n=7 Participants
|
79 participants
n=5 Participants
|
|
Photophobia
No
|
44 participants
n=5 Participants
|
42 participants
n=7 Participants
|
86 participants
n=5 Participants
|
|
Headache
Yes
|
70 participants
n=5 Participants
|
69 participants
n=7 Participants
|
139 participants
n=5 Participants
|
|
Headache
No
|
16 participants
n=5 Participants
|
10 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Pulsatile tinnitus
Yes
|
45 participants
n=5 Participants
|
41 participants
n=7 Participants
|
86 participants
n=5 Participants
|
|
Pulsatile tinnitus
No
|
41 participants
n=5 Participants
|
38 participants
n=7 Participants
|
79 participants
n=5 Participants
|
|
Perimetric mean deviation
Study eye
|
-3.5 dB
STANDARD_DEVIATION 1.2 • n=5 Participants
|
-3.5 dB
STANDARD_DEVIATION 1.1 • n=7 Participants
|
-3.5 dB
STANDARD_DEVIATION 1.1 • n=5 Participants
|
|
Perimetric mean deviation
Fellow eye
|
-2.3 dB
STANDARD_DEVIATION 1.1 • n=5 Participants
|
-2.3 dB
STANDARD_DEVIATION 1.1 • n=7 Participants
|
-2.3 dB
STANDARD_DEVIATION 1.1 • n=5 Participants
|
|
Papilledema grade (fundus photography) Study Eye
Study eye 1
|
8 participants
n=5 Participants
|
12 participants
n=7 Participants
|
20 participants
n=5 Participants
|
|
Papilledema grade (fundus photography) Study Eye
Study eye 2
|
32 participants
n=5 Participants
|
23 participants
n=7 Participants
|
55 participants
n=5 Participants
|
|
Papilledema grade (fundus photography) Study Eye
Study eye 3
|
20 participants
n=5 Participants
|
20 participants
n=7 Participants
|
40 participants
n=5 Participants
|
|
Papilledema grade (fundus photography) Study Eye
Study eye 4
|
24 participants
n=5 Participants
|
21 participants
n=7 Participants
|
45 participants
n=5 Participants
|
|
Papilledema grade (fundus photography) Study Eye
Study eye 5
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Papilledema grade (fundus photography) Fellow eye
Fellow eye 1
|
15 participants
n=5 Participants
|
14 participants
n=7 Participants
|
29 participants
n=5 Participants
|
|
Papilledema grade (fundus photography) Fellow eye
Fellow eye 2
|
33 participants
n=5 Participants
|
28 participants
n=7 Participants
|
61 participants
n=5 Participants
|
|
Papilledema grade (fundus photography) Fellow eye
Fellow eye 3
|
19 participants
n=5 Participants
|
21 participants
n=7 Participants
|
40 participants
n=5 Participants
|
|
Papilledema grade (fundus photography) Fellow eye
Fellow eye 4
|
19 participants
n=5 Participants
|
14 participants
n=7 Participants
|
33 participants
n=5 Participants
|
|
Papilledema grade (fundus photography) Fellow eye
Fellow eye 5
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
HIT-6 total score
|
60.3 units on a scale
STANDARD_DEVIATION 8.7 • n=5 Participants
|
59.1 units on a scale
STANDARD_DEVIATION 9.3 • n=7 Participants
|
59.7 units on a scale
STANDARD_DEVIATION 9.0 • n=5 Participants
|
|
CSF pressure
|
348.9 mm H2O
STANDARD_DEVIATION 94.1 • n=5 Participants
|
342.0 mm H2O
STANDARD_DEVIATION 70.7 • n=7 Participants
|
343.5 mm H2O
STANDARD_DEVIATION 86.9 • n=5 Participants
|
|
SF-36 component summary score
Physical
|
45.4 units on a scale
STANDARD_DEVIATION 9.8 • n=5 Participants
|
46.3 units on a scale
STANDARD_DEVIATION 8.2 • n=7 Participants
|
45.8 units on a scale
STANDARD_DEVIATION 9.0 • n=5 Participants
|
|
SF-36 component summary score
Mental
|
45.2 units on a scale
STANDARD_DEVIATION 9.8 • n=5 Participants
|
46.3 units on a scale
STANDARD_DEVIATION 8.2 • n=7 Participants
|
45.8 units on a scale
STANDARD_DEVIATION 9.0 • n=5 Participants
|
PRIMARY outcome
Timeframe: base line and 6 monthsPopulation: Sixty-nine of the 86 participants (80%) in the acetazolamide group completed follow-up compared with 57 of the 79 participants (72%) in the placebo group.
Treatment Effects on the Primary Outcome Variable, Mean change From Baseline to Month 6 in Perimetric Mean Deviation (PMD) in the Study Eye. Perimetric mean deviation is a measure of global visual field loss (mean deviation from age-corrected normal values), with a range of 2 to -32 dB; larger negative values indicate greater vision loss.
Outcome measures
| Measure |
Acetazolamide
n=69 Participants
Acetazolamide given in escalating doses
Acetazolamide: Subjects will begin with four 250 mg tablets daily.
|
Sugar Pill
n=57 Participants
Given in escalating "dose" (number of pill)
Placebo: Subjects will begin with four tablets daily.
|
|---|---|---|
|
Mean Change in Perimetric Mean Deviation
|
1.43 dB
Standard Error 0.24
|
0.71 dB
Standard Error 0.28
|
SECONDARY outcome
Timeframe: Baseline and 6 MonthsPopulation: Sixty-nine of the 86 participants (80%) in the acetazolamide group completed follow-up compared with 57 of the 79 participants (72%) in the placebo group.
Mean change at month 6 as compared to baseline. Frisén papilledema grade is an ordinal scale that uses ocular fundus features to rate the severity of papilledema; grade 0 indicates no features of papilledema and grade 5 indicates severe papilledema.
Outcome measures
| Measure |
Acetazolamide
n=69 Participants
Acetazolamide given in escalating doses
Acetazolamide: Subjects will begin with four 250 mg tablets daily.
|
Sugar Pill
n=57 Participants
Given in escalating "dose" (number of pill)
Placebo: Subjects will begin with four tablets daily.
|
|---|---|---|
|
Mean Change of Papilledema Grade on Fundus Photography
Study eye
|
-1.31 units on a scale
Standard Error 0.11
|
-0.61 units on a scale
Standard Error 0.11
|
|
Mean Change of Papilledema Grade on Fundus Photography
Fellow eye
|
-1.14 units on a scale
Standard Error 0.10
|
-0.52 units on a scale
Standard Error 0.11
|
SECONDARY outcome
Timeframe: baselineVisual Function Questionnaire (VFQ-25) total score, VFQ-25 10-item neuro-ophthalmic supplement total score: 0-100 (higher scores indicate better quality of life)
Outcome measures
| Measure |
Acetazolamide
n=86 Participants
Acetazolamide given in escalating doses
Acetazolamide: Subjects will begin with four 250 mg tablets daily.
|
Sugar Pill
n=79 Participants
Given in escalating "dose" (number of pill)
Placebo: Subjects will begin with four tablets daily.
|
|---|---|---|
|
Visual Function Questionnaire (VFQ-25)
10-item neuro-ophthalmic supplement
|
75.8 units on a scale
Standard Deviation 15.4
|
75.0 units on a scale
Standard Deviation 13.7
|
|
Visual Function Questionnaire (VFQ-25)
Total score
|
83.8 units on a scale
Standard Deviation 14.1
|
82.1 units on a scale
Standard Deviation 13.4
|
SECONDARY outcome
Timeframe: BaselineOutcome measures
| Measure |
Acetazolamide
n=86 Participants
Acetazolamide given in escalating doses
Acetazolamide: Subjects will begin with four 250 mg tablets daily.
|
Sugar Pill
n=79 Participants
Given in escalating "dose" (number of pill)
Placebo: Subjects will begin with four tablets daily.
|
|---|---|---|
|
Visual Acuity (No. of Correct Letters)
Study Eye
|
56.8 correct letters
Standard Deviation 5.1
|
55.6 correct letters
Standard Deviation 5.9
|
|
Visual Acuity (No. of Correct Letters)
Fellow Eye
|
58.3 correct letters
Standard Deviation 4.3
|
56.2 correct letters
Standard Deviation 6.4
|
Adverse Events
Acetazolamide
Serious events: 9 serious events
Other events: 80 other events
Deaths: 0 deaths
Sugar Pill
Serious events: 7 serious events
Other events: 67 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Acetazolamide
n=86 participants at risk
Acetazolamide given in escalating doses
Acetazolamide: Subjects will begin with four 250 mg tablets daily.
|
Sugar Pill
n=79 participants at risk
Given in escalating "dose" (number of pill)
Placebo: Subjects will begin with four tablets daily.
|
|---|---|---|
|
Eye disorders
Rapidly failing vision
|
0.00%
0/86
|
2.5%
2/79 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.00%
0/86
|
1.3%
1/79 • Number of events 1
|
|
Renal and urinary disorders
Renal impairment
|
1.2%
1/86 • Number of events 1
|
0.00%
0/79
|
|
Investigations
Transaminitis
|
1.2%
1/86 • Number of events 1
|
0.00%
0/79
|
|
Investigations
Elevated lipase with pancreatititis
|
1.2%
1/86 • Number of events 1
|
0.00%
0/79
|
|
Gastrointestinal disorders
Diverticulitis
|
1.2%
1/86 • Number of events 1
|
0.00%
0/79
|
|
Immune system disorders
Allergic reaction of unknown origin
|
1.2%
1/86 • Number of events 1
|
0.00%
0/79
|
|
Metabolism and nutrition disorders
Hypokalemia
|
1.2%
1/86 • Number of events 1
|
0.00%
0/79
|
|
Infections and infestations
Pyelonephritis
|
1.2%
1/86 • Number of events 1
|
0.00%
0/79
|
|
Pregnancy, puerperium and perinatal conditions
Live Birth
|
2.3%
2/86 • Number of events 2
|
0.00%
0/79
|
|
Renal and urinary disorders
Hydronephrosis
|
1.2%
1/86 • Number of events 1
|
0.00%
0/79
|
|
Surgical and medical procedures
Caesarean section
|
1.2%
1/86 • Number of events 1
|
0.00%
0/79
|
|
Ear and labyrinth disorders
Diplopia
|
0.00%
0/86
|
1.3%
1/79 • Number of events 1
|
|
Infections and infestations
Bronchitis
|
0.00%
0/86
|
1.3%
1/79 • Number of events 1
|
|
Injury, poisoning and procedural complications
Ventriculoperitoneal shunt malfunction
|
0.00%
0/86
|
1.3%
1/79 • Number of events 1
|
|
Nervous system disorders
Intracranial pressure increased
|
0.00%
0/86
|
1.3%
1/79 • Number of events 1
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/86
|
1.3%
1/79 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmnary embolism
|
0.00%
0/86
|
1.3%
1/79 • Number of events 1
|
|
Surgical and medical procedures
Ventriculo-peritoneal shunt
|
0.00%
0/86
|
1.3%
1/79 • Number of events 1
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/86
|
1.3%
1/79 • Number of events 1
|
Other adverse events
| Measure |
Acetazolamide
n=86 participants at risk
Acetazolamide given in escalating doses
Acetazolamide: Subjects will begin with four 250 mg tablets daily.
|
Sugar Pill
n=79 participants at risk
Given in escalating "dose" (number of pill)
Placebo: Subjects will begin with four tablets daily.
|
|---|---|---|
|
Hepatobiliary disorders
Elevated ALT
|
7.0%
6/86 • Number of events 6
|
3.8%
3/79 • Number of events 4
|
|
General disorders
Decreased CO2
|
10.5%
9/86 • Number of events 9
|
0.00%
0/79
|
|
Gastrointestinal disorders
Diarrhea
|
14.0%
12/86 • Number of events 14
|
3.8%
3/79 • Number of events 4
|
|
General disorders
Dizziness
|
9.3%
8/86 • Number of events 11
|
3.8%
3/79 • Number of events 4
|
|
General disorders
Dysgeusia
|
15.1%
13/86 • Number of events 13
|
0.00%
0/79
|
|
Gastrointestinal disorders
Dyspepsia
|
8.1%
7/86 • Number of events 8
|
1.3%
1/79 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
8.1%
7/86 • Number of events 8
|
2.5%
2/79 • Number of events 2
|
|
General disorders
Fatigue
|
16.3%
14/86 • Number of events 16
|
1.3%
1/79 • Number of events 1
|
|
General disorders
Headache
|
15.1%
13/86 • Number of events 17
|
13.9%
11/79 • Number of events 16
|
|
General disorders
Nasopharyngitis
|
5.8%
5/86 • Number of events 6
|
10.1%
8/79 • Number of events 11
|
|
General disorders
Nausea
|
30.2%
26/86 • Number of events 30
|
12.7%
10/79 • Number of events 10
|
|
Nervous system disorders
Paresthesia
|
47.7%
41/86 • Number of events 51
|
6.3%
5/79 • Number of events 6
|
|
Surgical and medical procedures
Post-LP syndrome
|
5.8%
5/86 • Number of events 9
|
7.6%
6/79 • Number of events 9
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.1%
7/86 • Number of events 8
|
2.5%
2/79 • Number of events 2
|
|
Infections and infestations
Sinusitis
|
3.5%
3/86 • Number of events 3
|
7.6%
6/79 • Number of events 7
|
|
Ear and labyrinth disorders
Tinnitus
|
12.8%
11/86 • Number of events 12
|
3.8%
3/79 • Number of events 3
|
|
General disorders
Vomiting
|
14.0%
12/86 • Number of events 13
|
3.8%
3/79 • Number of events 3
|
Additional Information
Dr. Michael Wall
University of Iowa Hospitals and Clinics
Phone: 319-353-3942
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place