Lawlor 2018 / NILVAD

Study ID(s) and Acronym(s)
NCT02017340 / NILVAD / NILVAD2012 / 2012-002764-27
Current Status of Trial
Completed
Study Aim
Treatment Dementia
Study Design
RCT
Blinding
Triple-blind
Intervention type
Pharmacological
Intervention
Nilvadipine // Placebo
Dosage and Duration
Arm 1: 8mg of Nilvadipine taken once a day at lunch time for 78 weeks // Arm 2: 8mg Placebo tablet taken once a day at lunch time for 78 weeks
Absolute Number of Participants
511
Health Status/Diagnosis
Alzheimer Disease (AD)
Main Diagnostic Criteria
Probable AD based on NINCDS-ADRDA criteria // Mini-Mental State Examination (SMMSE) score > 12 on stable dose (>3 months of cholinesterase inhibitor and or memantine) // Systolic BP > 100 mmHg but ≤ 159 mmHg, and diastolic BP > 65 mmHg but ≤ 99 mmHg on resting office based BP measurements, or a Systolic BP > 105 mmHg but ≤ 140 mmHg, and diastolic BP > 70 mmHg but ≤ 90 mmHg on ABPM measurement
Primary outcomes
Cognition (ADAS-Cog)
Other outcomes
Cognition (Sun of Boxes) // Disability Assessment for Dementia
Key Points
"The prespecified primary analyses failed to show any treatment benefit for nilvadipine on the co-primary outcome (p = 0.465). Decline from baseline in ADAS-Cog 12 on placebo was 0.79 (95% CI, -0.07-1.64) at 13 weeks, 6.41 (5.33-7.49) at 52 weeks, and 9.63 (8.33-10.93) at 78 weeks and on nilvadipine was 0.88 (0.02-1.74) at 13 weeks, 5.75 (4.66-6.85) at 52 weeks, and 9.41 (8.09-10.73) at 78 weeks. Exploratory analyses of the planned secondary outcomes showed no substantial effects, including on the CDR-sb or the Disability Assessment for Dementia. Nilvadipine appeared to be safe and well tolerated. Mortality was similar between groups (3 on nilvadipine, 4 on placebo); higher counts of adverse events (AEs) on nilvadipine (1,129 versus 1,030), and serious adverse events (SAEs; 146 versus 101), were observed. There were 14 withdrawals because of AEs. Major limitations of this study were that subjects had established dementia and the likelihood that non-Alzheimer subjects were included because of the lack of biomarker confirmation of the presence of brain amyloid." Lawlor 2018