GWPCARE4
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Clinical Question
In patients ages 2 to 55 with Lennox-Gastaut syndrome (LGS), how does the efficacy and safety of cannibidiol compare to placebo as add-on therapy to existing anti-epileptics?
Bottom Line
Using cannibidiol as add-on therapy reduced the number of drop seizures, non-drop seizures, and total seizures in patients with LGS who are refractory to other anti-epileptics.
Major Points
Guidelines
Design
- Multicenter, double-blind, placebo-controlled trial
- N=171
- Cannibidiol (n=86)
- Placebo (n=85)
- Setting: 31 sites in the US, Netherlands, and Poland
- Enrollment: April 2015 to October 2015
- Analysis: ITT
- Primary outcome: percentage change in monthly frequency of drop seizures from baseline
Population
Inclusion Criteria
- 2 to 55 years old with diagnosis of LGS
- Evidence of more than one type of generalized seizure for at least 6 months
- Refractory to at least 2 anti-epileptics
- Patients taking 1 to 4 anti-epileptic drugs and had at least 2 drop seizures per week
Exclusion Criteria
- Unstable illness other than epilepsy
- History or alcohol or substance misuse
- Recreational cannabis users
- Positive THC screen
Baseline Characteristics
- Mean age: 72 years
- Mean BMI: 28
- Mean HbA1c: 8.8%
- Units of insulin: 14 units/day
Interventions
- Randomized to intensive (targeting HbA1c <6%) or standard (HbA1c 7-7.9%) glycemic therapy
- Then 46% were randomized to intensive (SBP <120) vs. standard (SBP <140) blood pressure therapy
- Remaining 54% randomized to fenofibrate vs. placebo; all received statin
- Intensive glycemic control group attended monthly visits for 4 months, then every 2 months, with additional visits and telephone calls as needed
- Standard therapy group had glycemic control visits every 4 months
Outcomes
Comparisons are intensive therapy vs. standard therapy.
Primary Outcomes
- Annual rate of nonfatal MI or nonfatal stroke or cardiovascular death
- 2.11% vs. 2.29% (HR 0.90; 95% CI 0.78-1.04; P=0.16)
Secondary Outcomes
- Annual rate of death from any cause
- 1.41% vs. 1.14% (HR 1.22; 95% CI 1.01-1.46; P=0.04)
- Annual rate of cardiovascular death
- 0.79% vs. 0.56% (HR 1.35; 95% CI 1.04-1.76; P=0.02)