Trial Outcomes & Findings for Valproate in Dementia (VALID) (NCT NCT00071721)
NCT ID: NCT00071721
Last Updated: 2014-09-25
Results Overview
NPI quantifies behavioral changes in dementia, including depression, anxiety, psychosis, agitation, and others. This is a questionnaire administered to the subject's study partner. The range of this instrument is 0 to 120 with higher numbers indicating greater impairment. To determine whether or not psychosis or agitation is present, there is no cutoff score but is based on the clinician's judgment. In the NPI, the subject responds to 'Yes' or 'No' questions. Then it is determined how often psychosis or agitation occurs and if it is mild, moderate or severe.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
313 participants
Primary outcome timeframe
24 months
Results posted on
2014-09-25
Participant Flow
Participant milestones
| Measure |
Valproate
250mg tablets beginning with one daily for one week, then two daily for one week, then titrated according to body weight and tolerability to achieve 10-12 mg/kg daily for 2 years, followed by a 2-month washout
|
Placebo
Placebo tablets beginning with one daily and increasing according to weight and perceived tolerability concerns for two years, followed by a 2-month washout
|
|---|---|---|
|
Overall Study
STARTED
|
153
|
160
|
|
Overall Study
COMPLETED
|
81
|
69
|
|
Overall Study
NOT COMPLETED
|
72
|
91
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Valproate in Dementia (VALID)
Baseline characteristics by cohort
| Measure |
Valproate
n=153 Participants
250mg tablets beginning with one daily for one week, then two daily for one week, then titrated according to body weight and tolerability to achieve 10-12 mg/kg daily for 2 years, followed by a 2-month washout
|
Placebo
n=160 Participants
Placebo tablets beginning with one daily and increasing according to weight and perceived tolerability concerns for two years, followed by a 2-month washout
|
Total
n=313 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
74.9 years
STANDARD_DEVIATION 8.2 • n=5 Participants
|
76.6 years
STANDARD_DEVIATION 7.4 • n=7 Participants
|
75.7 years
STANDARD_DEVIATION 7.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
83 Participants
n=5 Participants
|
101 Participants
n=7 Participants
|
184 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
70 Participants
n=5 Participants
|
59 Participants
n=7 Participants
|
129 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
153 participants
n=5 Participants
|
160 participants
n=7 Participants
|
313 participants
n=5 Participants
|
|
ADAScog
|
29.4 Units on a scale
STANDARD_DEVIATION 8.9 • n=5 Participants
|
30.1 Units on a scale
STANDARD_DEVIATION 9.8 • n=7 Participants
|
29.8 Units on a scale
STANDARD_DEVIATION 9.4 • n=5 Participants
|
|
ADCS-ADL
|
56.9 Units on a scale
STANDARD_DEVIATION 11.8 • n=5 Participants
|
54.9 Units on a scale
STANDARD_DEVIATION 13 • n=7 Participants
|
55.9 Units on a scale
STANDARD_DEVIATION 12.4 • n=5 Participants
|
|
CDR-SOB
|
7.1 Units on a scale
STANDARD_DEVIATION 2.7 • n=5 Participants
|
7.5 Units on a scale
STANDARD_DEVIATION 3.1 • n=7 Participants
|
7.3 Units on a scale
STANDARD_DEVIATION 2.9 • n=5 Participants
|
|
CMAI
|
10.9 Units on a scale
STANDARD_DEVIATION 8.9 • n=5 Participants
|
11.9 Units on a scale
STANDARD_DEVIATION 10.4 • n=7 Participants
|
11.4 Units on a scale
STANDARD_DEVIATION 9.7 • n=5 Participants
|
|
NPI
|
2.6 Units on a scale
STANDARD_DEVIATION 2.6 • n=5 Participants
|
3.1 Units on a scale
STANDARD_DEVIATION 2.6 • n=7 Participants
|
2.9 Units on a scale
STANDARD_DEVIATION 2.6 • n=5 Participants
|
PRIMARY outcome
Timeframe: 24 monthsNPI quantifies behavioral changes in dementia, including depression, anxiety, psychosis, agitation, and others. This is a questionnaire administered to the subject's study partner. The range of this instrument is 0 to 120 with higher numbers indicating greater impairment. To determine whether or not psychosis or agitation is present, there is no cutoff score but is based on the clinician's judgment. In the NPI, the subject responds to 'Yes' or 'No' questions. Then it is determined how often psychosis or agitation occurs and if it is mild, moderate or severe.
Outcome measures
| Measure |
Valproate
n=153 Participants
250mg tablets beginning with one daily for one week, then two daily for one week, then titrated according to body weight and tolerability to achieve 10-12 mg/kg daily for 2 years, followed by a 2-month washout
|
Placebo
n=160 Participants
Placebo tablets beginning with one daily and increasing according to weight and perceived tolerability concerns for two years, followed by a 2-month washout
|
|---|---|---|
|
Presence of Agitation and/or Psychosis Measured by the Neuropsychiatric Inventory (NPI) Combined With an Assessment of the Clinical Significance of Behavioral Change Rated by the Study Clinician
|
25 Participants
|
29 Participants
|
SECONDARY outcome
Timeframe: 24 monthsAlzheimer's Disease Assessment Scale, cognitive sub-scale in points per year (ADAS-cog) is a psychometric measure sensitive to change in mild to moderate AD. The range of this instrument is 0 to 70 with higher numbers indicating greater impairment.
Outcome measures
| Measure |
Valproate
n=153 Participants
250mg tablets beginning with one daily for one week, then two daily for one week, then titrated according to body weight and tolerability to achieve 10-12 mg/kg daily for 2 years, followed by a 2-month washout
|
Placebo
n=160 Participants
Placebo tablets beginning with one daily and increasing according to weight and perceived tolerability concerns for two years, followed by a 2-month washout
|
|---|---|---|
|
Cognitive Performance Assessed by the Alzheimer's Disease Assessment Scale-cognitive Subtest (ADAS-cog)
|
42.3 Units on a scale
Standard Deviation 14.3
|
41.9 Units on a scale
Standard Deviation 14.4
|
SECONDARY outcome
Timeframe: 24 monthsAlzheimer's Disease Cooperative Study Activities of Daily Living Score (ADCS-ADL) is a structured questionnaire about activities of daily living, administered to the subject's caregiver/study partner. The range of this instrument is 0 to 78 with lower numbers indicating greater impairment.
Outcome measures
| Measure |
Valproate
n=153 Participants
250mg tablets beginning with one daily for one week, then two daily for one week, then titrated according to body weight and tolerability to achieve 10-12 mg/kg daily for 2 years, followed by a 2-month washout
|
Placebo
n=160 Participants
Placebo tablets beginning with one daily and increasing according to weight and perceived tolerability concerns for two years, followed by a 2-month washout
|
|---|---|---|
|
Functional Performance Assessed by the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory
|
35.1 Units on a scale
Standard Deviation 20.3
|
41.0 Units on a scale
Standard Deviation 14.81
|
SECONDARY outcome
Timeframe: 24 monthsClinical Dementia Rating, Sum of Boxes (CDR-SOB) is a global rating of dementia severity based on the clinician's interpretation of the history and examination. The range of this instrument is 0 to 18 with higher numbers indicating greater impairment.
Outcome measures
| Measure |
Valproate
n=153 Participants
250mg tablets beginning with one daily for one week, then two daily for one week, then titrated according to body weight and tolerability to achieve 10-12 mg/kg daily for 2 years, followed by a 2-month washout
|
Placebo
n=160 Participants
Placebo tablets beginning with one daily and increasing according to weight and perceived tolerability concerns for two years, followed by a 2-month washout
|
|---|---|---|
|
Global Severity of Dementia Using the CDR Sum of Boxes
|
12.0 Units on a scale
Standard Deviation 4.1
|
11.5 Units on a scale
Standard Deviation 3.7
|
SECONDARY outcome
Timeframe: 24 monthsThe Cohen-Mansfield Agitation Inventory (CMAI) is a 29-item caregiver rating questionnaire for the assessment of agitation in older persons. It includes descriptions of 29 agitated behaviors, each rated on a 7-point scale of frequency. The range of this instrument is 29 to 203 with higher numbers indicating greater impairment.
Outcome measures
| Measure |
Valproate
n=153 Participants
250mg tablets beginning with one daily for one week, then two daily for one week, then titrated according to body weight and tolerability to achieve 10-12 mg/kg daily for 2 years, followed by a 2-month washout
|
Placebo
n=160 Participants
Placebo tablets beginning with one daily and increasing according to weight and perceived tolerability concerns for two years, followed by a 2-month washout
|
|---|---|---|
|
Agitation Measured by the Cohen-Mansfield Agitation Inventory (CMAI), Community Version
|
10.6 Units on a scale
Standard Deviation 11.6
|
12.1 Units on a scale
Standard Deviation 10.9
|
SECONDARY outcome
Timeframe: 24 monthsADCS-Clinical Global Impression of Change (ADCS-CGIC) provides a means to reliably assess global change from baseline. It provides a semi-structured format to allow clinicians to gather necessary clinical information from both the participant and informant, in order to make an overall impression of clinical change. The range of this instrument is 1 to 7 with lower numbers indicating improvement and higher numbers indicating a worsened state.
Outcome measures
| Measure |
Valproate
n=153 Participants
250mg tablets beginning with one daily for one week, then two daily for one week, then titrated according to body weight and tolerability to achieve 10-12 mg/kg daily for 2 years, followed by a 2-month washout
|
Placebo
n=160 Participants
Placebo tablets beginning with one daily and increasing according to weight and perceived tolerability concerns for two years, followed by a 2-month washout
|
|---|---|---|
|
Participant's Clinical Condition or Endpoint Assessed With the ADCS-Clinical Global Impression of Change (ADCS-CGIC)
|
5.7 Units on a scale
Standard Deviation 0.9
|
5.5 Units on a scale
Standard Deviation 1.1
|
Adverse Events
Valproate
Serious events: 51 serious events
Other events: 145 other events
Deaths: 0 deaths
Placebo
Serious events: 62 serious events
Other events: 151 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Valproate
n=153 participants at risk
250mg tablets beginning with one daily for one week, then two daily for one week, then titrated according to body weight and tolerability to achieve 10-12 mg/kg daily for 2 years, followed by a 2-month washout
|
Placebo
n=160 participants at risk
Placebo tablets beginning with one daily and increasing according to weight and perceived tolerability concerns for two years, followed by a 2-month washout
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Gastrointestinal disorders
Abdominal pain
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Psychiatric disorders
Abnormal behaviour
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Psychiatric disorders
Agitation
|
0.00%
0/153
|
1.2%
2/160 • Number of events 2
|
|
Blood and lymphatic system disorders
Anaemia
|
0.65%
1/153 • Number of events 1
|
1.2%
2/160 • Number of events 2
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Cardiac disorders
Angina unstable
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
2.0%
3/153 • Number of events 4
|
0.62%
1/160 • Number of events 2
|
|
Surgical and medical procedures
Bladder repair
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Surgical and medical procedures
Breast reconstruction
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Reproductive system and breast disorders
Breast swelling
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Infections and infestations
Bronchitis
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Cardiac disorders
Cardiac disorder
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/153
|
0.62%
1/160 • Number of events 2
|
|
Surgical and medical procedures
Cardiac pacemaker replacement
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Infections and infestations
Cellulitis
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Nervous system disorders
Cerebral artery occlusion
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
General disorders
Chest pain
|
2.0%
3/153 • Number of events 3
|
0.62%
1/160 • Number of events 1
|
|
Surgical and medical procedures
Cholecystectomy
|
0.65%
1/153 • Number of events 1
|
0.62%
1/160 • Number of events 1
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Chondropathy
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Psychiatric disorders
Confusional state
|
1.3%
2/153 • Number of events 2
|
0.00%
0/160
|
|
Nervous system disorders
Convulsion
|
0.00%
0/153
|
2.5%
4/160 • Number of events 4
|
|
Nervous system disorders
Coordination abnormal
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
General disorders
Death
|
3.3%
5/153 • Number of events 5
|
4.4%
7/160 • Number of events 7
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Vascular disorders
Deep vein thrombosis
|
0.65%
1/153 • Number of events 2
|
0.00%
0/160
|
|
Metabolism and nutrition disorders
Dehydration
|
2.0%
3/153 • Number of events 3
|
0.00%
0/160
|
|
Psychiatric disorders
Delirium
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Nervous system disorders
Depressed level of consciousness
|
0.65%
1/153 • Number of events 1
|
0.62%
1/160 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
1.3%
2/153 • Number of events 2
|
0.62%
1/160 • Number of events 1
|
|
Injury, poisoning and procedural complications
Drug toxicity
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Gastrointestinal disorders
Dysphagia
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.65%
1/153 • Number of events 1
|
1.9%
3/160 • Number of events 3
|
|
Infections and infestations
Enterococcal bacteraemia
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Gastrointestinal disorders
Faecaloma
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Injury, poisoning and procedural complications
Fall
|
3.9%
6/153 • Number of events 6
|
5.6%
9/160 • Number of events 10
|
|
Gastrointestinal disorders
Femoral hernia
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fractured sacrum
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Surgical and medical procedures
Gallbladder operation
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/153
|
1.2%
2/160 • Number of events 2
|
|
Renal and urinary disorders
Haematuria
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Psychiatric disorders
Hallucination
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Injury, poisoning and procedural complications
Head injury
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Hepatobiliary disorders
Hepatic mass
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Surgical and medical procedures
Hip arthroplasty
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/153
|
1.2%
2/160 • Number of events 2
|
|
Surgical and medical procedures
Hospitalisation
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Vascular disorders
Hypertension
|
0.65%
1/153 • Number of events 1
|
0.62%
1/160 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Vascular disorders
Hypotension
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Infections and infestations
Infection
|
0.00%
0/153
|
1.2%
2/160 • Number of events 2
|
|
Infections and infestations
Influenza
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Surgical and medical procedures
Joint arthroplasty
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Infections and infestations
Kidney infection
|
1.3%
2/153 • Number of events 2
|
0.00%
0/160
|
|
Surgical and medical procedures
Knee operation
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Surgical and medical procedures
Leg amputation
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Surgical and medical procedures
Lesion excision
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Psychiatric disorders
Lethargy
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Infections and infestations
Listeriosis
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Investigations
Liver function test abnormal
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Nervous system disorders
Lumbar radiculopathy
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Mantle cell lymphoma
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Psychiatric disorders
Mental disorder
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic neoplasm
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Gastrointestinal disorders
Oesophageal obstruction
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Infections and infestations
Pneumonia
|
3.3%
5/153 • Number of events 5
|
3.8%
6/160 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Infections and infestations
Pneumonia bacterial
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Infections and infestations
Postoperative infection
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Vascular disorders
Pulmonary embolism
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
General disorders
Pyrexia
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Musculoskeletal and connective tissue disorders
Spondylolisthesis
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Nervous system disorders
Subdural haematoma
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.65%
1/153 • Number of events 2
|
0.00%
0/160
|
|
Nervous system disorders
Subdural haemorrhage
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Surgical and medical procedures
Surgery
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Nervous system disorders
Syncope
|
2.6%
4/153 • Number of events 4
|
1.2%
2/160 • Number of events 2
|
|
Vascular disorders
Thrombosis
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Nervous system disorders
Transient ischaemic attack
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Renal and urinary disorders
Urinary incontinence
|
0.65%
1/153 • Number of events 1
|
0.00%
0/160
|
|
Renal and urinary disorders
Urinary retention
|
0.65%
1/153 • Number of events 1
|
0.62%
1/160 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
2.6%
4/153 • Number of events 5
|
1.9%
3/160 • Number of events 3
|
|
Surgical and medical procedures
Uterine prolapse repair
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Surgical and medical procedures
Ventriculo-peritoneal shunt
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
|
Surgical and medical procedures
Whole blood transfusion
|
0.00%
0/153
|
0.62%
1/160 • Number of events 1
|
Other adverse events
| Measure |
Valproate
n=153 participants at risk
250mg tablets beginning with one daily for one week, then two daily for one week, then titrated according to body weight and tolerability to achieve 10-12 mg/kg daily for 2 years, followed by a 2-month washout
|
Placebo
n=160 participants at risk
Placebo tablets beginning with one daily and increasing according to weight and perceived tolerability concerns for two years, followed by a 2-month washout
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
10.5%
16/153 • Number of events 19
|
8.1%
13/160 • Number of events 13
|
|
Psychiatric disorders
Agitation
|
28.1%
43/153 • Number of events 50
|
33.8%
54/160 • Number of events 74
|
|
Psychiatric disorders
Anxiety
|
15.7%
24/153 • Number of events 29
|
23.8%
38/160 • Number of events 47
|
|
Psychiatric disorders
Apathy
|
5.9%
9/153 • Number of events 9
|
5.6%
9/160 • Number of events 9
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
13.1%
20/153 • Number of events 21
|
7.5%
12/160 • Number of events 14
|
|
General disorders
Asthenia
|
31.4%
48/153 • Number of events 52
|
21.9%
35/160 • Number of events 37
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.7%
21/153 • Number of events 21
|
12.5%
20/160 • Number of events 20
|
|
Infections and infestations
Bronchitis
|
4.6%
7/153 • Number of events 8
|
3.1%
5/160 • Number of events 6
|
|
General disorders
Chest pain
|
4.6%
7/153 • Number of events 9
|
5.0%
8/160 • Number of events 8
|
|
Psychiatric disorders
Confusional state
|
49.7%
76/153 • Number of events 114
|
49.4%
79/160 • Number of events 111
|
|
Gastrointestinal disorders
Constipation
|
17.0%
26/153 • Number of events 28
|
8.1%
13/160 • Number of events 16
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.7%
21/153 • Number of events 24
|
11.2%
18/160 • Number of events 22
|
|
Psychiatric disorders
Crying
|
15.0%
23/153 • Number of events 27
|
13.8%
22/160 • Number of events 24
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.2%
8/153 • Number of events 9
|
4.4%
7/160 • Number of events 8
|
|
Psychiatric disorders
Delusion
|
6.5%
10/153 • Number of events 11
|
8.8%
14/160 • Number of events 20
|
|
Psychiatric disorders
Depressed mood
|
22.9%
35/153 • Number of events 37
|
14.4%
23/160 • Number of events 26
|
|
Psychiatric disorders
Depression
|
11.8%
18/153 • Number of events 19
|
6.2%
10/160 • Number of events 11
|
|
Gastrointestinal disorders
Diarrhoea
|
24.8%
38/153 • Number of events 45
|
11.9%
19/160 • Number of events 24
|
|
Nervous system disorders
Disturbance in attention
|
26.1%
40/153 • Number of events 40
|
24.4%
39/160 • Number of events 39
|
|
Nervous system disorders
Dizziness
|
15.0%
23/153 • Number of events 25
|
18.8%
30/160 • Number of events 36
|
|
Gastrointestinal disorders
Dry mouth
|
10.5%
16/153 • Number of events 16
|
9.4%
15/160 • Number of events 15
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
12.4%
19/153 • Number of events 20
|
5.6%
9/160 • Number of events 9
|
|
Gastrointestinal disorders
Faecal incontinence
|
5.2%
8/153 • Number of events 8
|
3.1%
5/160 • Number of events 5
|
|
Injury, poisoning and procedural complications
Fall
|
35.3%
54/153 • Number of events 85
|
26.2%
42/160 • Number of events 86
|
|
Nervous system disorders
Gait disturbance
|
33.3%
51/153 • Number of events 64
|
18.8%
30/160 • Number of events 35
|
|
Psychiatric disorders
Hallucination
|
5.9%
9/153 • Number of events 11
|
3.1%
5/160 • Number of events 5
|
|
Nervous system disorders
Headache
|
10.5%
16/153 • Number of events 19
|
8.1%
13/160 • Number of events 16
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
2.6%
4/153 • Number of events 4
|
5.6%
9/160 • Number of events 9
|
|
Psychiatric disorders
Insomnia
|
13.1%
20/153 • Number of events 23
|
10.0%
16/160 • Number of events 18
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
9.2%
14/153 • Number of events 15
|
6.2%
10/160 • Number of events 12
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
18.3%
28/153 • Number of events 32
|
8.8%
14/160 • Number of events 14
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.2%
11/153 • Number of events 12
|
6.9%
11/160 • Number of events 12
|
|
Infections and infestations
Nasopharyngitis
|
7.2%
11/153 • Number of events 12
|
5.6%
9/160 • Number of events 13
|
|
Gastrointestinal disorders
Nausea
|
9.2%
14/153 • Number of events 16
|
6.2%
10/160 • Number of events 11
|
|
General disorders
Oedema peripheral
|
6.5%
10/153 • Number of events 12
|
4.4%
7/160 • Number of events 7
|
|
Renal and urinary disorders
Pollakiuria
|
15.0%
23/153 • Number of events 25
|
10.6%
17/160 • Number of events 19
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.6%
7/153 • Number of events 7
|
9.4%
15/160 • Number of events 17
|
|
Psychiatric disorders
Restlessness
|
18.3%
28/153 • Number of events 34
|
19.4%
31/160 • Number of events 39
|
|
Psychiatric disorders
Somnolence
|
43.1%
66/153 • Number of events 80
|
28.7%
46/160 • Number of events 51
|
|
Nervous system disorders
Tremor
|
28.8%
44/153 • Number of events 51
|
13.8%
22/160 • Number of events 23
|
|
Renal and urinary disorders
Urinary incontinence
|
9.8%
15/153 • Number of events 18
|
9.4%
15/160 • Number of events 16
|
|
Infections and infestations
Urinary tract infection
|
9.8%
15/153 • Number of events 19
|
10.6%
17/160 • Number of events 28
|
|
Eye disorders
Vision blurred
|
6.5%
10/153 • Number of events 11
|
5.0%
8/160 • Number of events 8
|
|
Gastrointestinal disorders
Vomiting
|
5.9%
9/153 • Number of events 10
|
4.4%
7/160 • Number of events 7
|
|
Investigations
Weight decreased
|
7.2%
11/153 • Number of events 12
|
6.9%
11/160 • Number of events 11
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place