Here are some notes on many of the clinical trials in neurology organized in various ways by condition. The evidence generated from clinical trials has pushed our field forwards and allowed neurologists to improve the lives of thousands of patients. This section helps as a study quick reference or as a starting point for further study. Please go to the original trials that interest you for the details and more in-depth study. Hope you find it useful!
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Please see disclaimer for details. None of this information is medical advice or endorsement for practicing medicine a certain way. These are merely a study aid. This list was started offline in 2003 and has been updated intermittently since then. It is still useful as a study aid so it is included here.
Clinical Trials in Neurology:
Thrombectomy devices, Stentretrivers vs. MERCI trials:
Study | Window/ Eligibility feature |
LVO determination | Intervention | Comparison | Outcome | Result |
SWIFT 2012 |
8hrs NIHSS |
Yes | Solitaire | MERCI | TIMI ≥2 | N=113 61%vs 24% OR 4·87 [95% CI 2·14-11·10]; p=0·0001 |
TREVO 2012 |
8hrs NIHSS 8-29 |
Yes | Trevo | MERCI | TICI ≥2 | N= 90 86% vs. 60% OR 4·22, 95% CI 1·92-9·69; p<0·0001 |
References:
- Saver JL, et al SWIFT Trialists. Lancet. 2012 Oct 6;380(9849):1241-9.
- Nogueira RG, et al. TREVO 2 Trialists. Lancet. 2012 Oct 6;380(9849):1231-40.
First Generation Endovascular Stroke Intervention trials:
Study | Window/ Eligibility feature |
LVO determination | Intervention | Comparison | Outcome | Result |
PROACT 1999 |
<6hr | Yes | IA TPA | IV heparin | mRS ≤2 at 90 days | n=180 40% vs. 25% P=0.4 sICH 10% vs. 2 % p=0.06 |
IMS III 2013 |
<3-4.5hrs But IAT in 6hr |
Not universal CTA or clinical |
IV TPA +IAT: (IA TPA, MERCI) |
IV TPA | mRS ≤2 at 90 days | n= 656 40.8% vs 38.7% CI, -6.1 to 9.1 sICH 6.2% v 5.9% |
MR RESCUE 2013 |
<8 hr | Yes Anterior cir |
MERCI/Penumbra | Standard care (IV TPA or aspirin) | Mean mRS at 90 days | n= 118 3.9 vs 3.9 Mortality 21%, sICH 4% both groups No interaction: treatment w penumbral pattern |
Synthesis 2013 |
<4.5hr But IAT in 6hr |
No | IAT: (IA TPA full dose, MERCI) +Heparin 5000 IU bolus & 500iu/hr |
IV TPA | mRS ≤1 at 90 days | n=362 30.4% vs. 34.8% sICH 6% v 6% |
References:
- Furlan A, et al PROACT II. JAMA. 1999 Dec 1;282(21):2003-11.
- Broderick JP, et al, IMS III. N Engl J Med. 2013 Mar 7;368(10):893-903.
- Kidwell CS, et al MR RESCUE. N Engl J Med. 2013 Mar 7;368(10):914-23.
- Ciccone A, et al; SYNTHESIS. N Engl J Med. 2013 Jun 20;368(25):2433-4.
Second Generation Endovascular Stroke Intervention trials:
Study | Window/ Eligibility feature |
LVO determination | Intervention | Comp. | Outcome | Result |
MR CLEAN 2014 |
≤6hr | Yes (ICA MCA) CTA | Stent-retriever* +IV TPA |
IV TPA | mRS at 90 days | n=500 32.6% vs 19.1% OR 1.67 CI 1.21 to 2.3 No difference sICH |
ESCAPE 2015 |
≤12hr MultiphaseCTA |
Yes (ICA MCA) CTA |
Stent-retriever* +IV TPA | IV TPA | mRS at 90 days | n=316 53.0%, vs. 29.3% OR 2.6; CI, 1.7 to 3.8; P<0.001 Death 10.4% vs 19% p=0.04 sICH 3.6 vs 2.7% |
REVASCAT 2015 |
≤8hr IV TPA failure Or IV TPA contraindicated |
Yes (ICA MCA) CTA |
Stent-retriever +/-IV TPA | IV TPA | mRS (shift analysis) at 90 days mRS (0-2) at 90 days |
n=206 OR 1.7; CI 1.05-2.8 mRS 0-2: 43.7% vs. 28.2% sICH 1.9% in both groups Death 18.4% vs 15.5% |
EXTEND IA 2015 |
≤4.5hr 6hr IAT CTP core <70ml |
Yes (ICA MCA) CTA |
Solitaire +IV TPA | IV TPA | Reperfusion @24 & early neuro Improvement | n=70 Reperfusion: 100% vs. 37% p<0.001 Early imprv: 80% v 37% mRS 71% vs. 40% p=0.01 sICH & mortality no difference |
SWIFT PRIME 2015 |
≤4.5hr 6hr IAT CTP small core 50ml (71pts) ASPECTS ≥6 (125pts) |
Yes (ICA MCA) CTA |
Solitaire +IV TPA | IV TPA | mRS 0-2 at 90 days | n=196 60% vs. 35%, p<0.001 Mortality 9% vs. 12% sICH 0% vs. 3% |
References:
- Berkhemer OA, et al; MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015 Jan 1;372(1):11-20. doi: 10.1056/NEJMoa1411587. Epub 2014 Dec 17.
- Goyal M, et al.; ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015 Mar 12;372(11):1019-30. doi: 10.1056/NEJMoa1414905. Epub 2015 Feb 11.
- Campbell BC, et al; EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015 Mar 12;372(11):1009-18. doi: 10.1056/NEJMoa1414792. Epub 2015 Feb 11.
- Saver JL, et al; SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015 Jun 11;372(24):2285-95. doi: 10.1056/NEJMoa1415061. Epub 2015 Apr 17.
- Jovin TG, et al.; REVASCAT Trial Investigators. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015 Jun 11;372(24):2296-306. doi: 10.1056/NEJMoa1503780. Epub 2015 Apr 17.
Number Needed to Treat for Benefit- NNTB for Endovascular Stroke Intervention:
For mRS 0-2 (functional independence):
- NNTB= 4, ESCAPE
- NNTB= 4, SWIFT PRIME
- NNTB= 7, MR CLEAN
- NNTB= 7, REVASCAT
For mRS shift i.e. improvement on mRS:
- NNTB ~3, ESCAPE
- NNTB 4, MR CLEAN
IV TPA for mRS 0-1:
- NNTB 8-15, depending on time to treatment
Epilepsy Clinical Trials:
Study | Year | Patients/Population | Intervention | Comparison | Outcome | Results | Study design | Comment |
---|---|---|---|---|---|---|---|---|
EO3 study | 1994 | Patients with refractory epilpesy with partial seizures | Therapeutic VNS paradigm | Less or non-therapeutic VNS paradigm | Mean seizure frequency percentage reduction, 50% seizure frequency reduction, |
30.9% vs. 11.3%, p=0.029. For 50% seizure reduction: 38.7% vs. 19.4%. |
RCT | |
Handforth A et al. | 1998 | Patients with refractory epilpesy with partial seizures | High VNS settings | Low VNS settings | Percentage change in total seizure frequency compared with baseline | 28% vs. 15%, p=0.04 | RCT | |
D’Onofrio G, et al | 1999 | Patients with Chronic alcohol abuse, GTCS seizure in the ER | Lorazepam 2mg | Placebo | Seizure recurrence in ER observation period | n=186, 3% vs. 24% had second seizure, OR 10.4, CI 3.6-30.2; p<0.001. Hospital admission was 42% vs. 24%, OR 2.1 CI 1.1-4; P=0.02 |
RCT | |
Daeppen JB et al. | 2002 | Patients with alcohol dependence admitted to the hospital | Symptom triggered: oxazepam in response to withdrawal symptoms | Fixed-schedule: oxazepam every 6 hours with additional doses as needed | Total amount and duration of treatment with oxazepam, the incidence of complications, and the comfort level. |
n=117, Patients treated with oxazepam: 39% vs. 100%, p<0.001. Mean oxazepam dose 37.5mg vs. 231.4 mg. Mean duration of treatment 20hrs vs. 62.7 hrs p<0.001. Complications: single seizure in symptom triggered group. Comfort level: no different. |
RCT | |
Hessen E, et al | 2006 | Seizure free for >2 years on monotherapy | Withdrawal of AED | Continuation of AED | Cognitive function by California Computerized assessment package | Cognitive processing speed 24 vs 43 ms. No change in attention or reaction time. |
RCT | Most patients were on carbamazepine and Valproic acid |
Akershus Study | 2007 | Seizure free patients for >2 years on monotherapy | AED withdrawal | non-AED withdrawal | Cognitive functions, seizure relapse, health-related quality of life (HRQOL), and EEG result |
n=160, seizure relapse at 12 months 15% vs. 7%, RR 2.46, CI 0.85-7.08, p=0.095. Normal neuropsychological testing was 28% vs. 11%. No change in quality of life or EEG. |
RCT | Multiple outcomes were assessed instead of determining power and design for a main primary outcome |
SANAD trial | 2007 | Patients with Idiopathic generalized epilepsy or unclassified epilepsy | Valproic acid | Lamotrigine or topiramate | time to treatment failure, and time to 1-year remission |
Time to treatment failure VPA better than topiramate HR 1·57 CI 1·19–2·08. VPA was similar to lamotrigine. For IGE valproic acid was better than lamotringe HR 1·55 CI 1·07–2·24 and topiramate HR 1·89 CI 1·32–2·70 |
RCT | Valproic acid was better tolerated than topiramate, and more efficacious than lamotrigine for idiopathic generalized epilepsy |
SANAD trial partial | 2007 | Patients with partial epilepsy | Carbamazepine | Gabapentin, lamotrigine, oxcarbazepine, or topiramate | Time to treatment failure, and time to 12-months remission | Lamotrigine was better than carbamazepine HR 0.78 CI 0.63-0.97 gabapentin HR 0.65 CI 0.52-0.80, and topiramate HR 0.64 CI 0.52-0.79. Not significantly better than oxcarbazepine HR 1.15 CI 0.86-1.54. Time to 12-month remission carbamazepine was significantly better than gabapentin HR 0.75 CI 0.63-0.90, not significantly different that lamotrigine, topiramate, or oxcarbazepine. |
RCT, unblinded | Lamotrigine was better than carbamazepine |
Neal EG et al. | 2008 | Children with medically refractory epilepsy | Immediate ketogenic diet | Ketogenic diet after 3 months | Reduction in seizures as measured by 50% reduction in seizures | n=103, 38% vs. 6%, p<0.0001 | RCT, unblinded | Levetiracetam was not superior to valproic acid or carbamazepine |
RAMPART | 2012 | Status epilepticus pre-hospital | Midazolam intramuscular | Lorazepam Intravenous | Absence of seizures at ER arrival | 73.4% vs. 63.4%, 95% CI. 4 to 16.1; p<0.001, noninferiority and superiority Intubation in 14.1% vs. 14.4% |
RCT | |
KOMET study | 2012 | Patients with newly diagnosed epilepsy | Levetiracetam | Valproic acid or carbamazepine | Time to withdrawal from study medication (treatment withdrawal) |
not significantly different HR (95% CI) 0.90 (0.74 to 1.08). Also similar seizure and adverse events. |
RCT, unblinded superiority | Levetiracetam was not superior to valproic acid or carbamazepine |
References:
- Silbergleit R, et al; NETT Investigators. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012 Feb 16;366(7):591-600. doi: 10.1056/NEJMoa1107494.
- Hessen E, et al. Influence of major antiepileptic drugs on attention, reaction time, and speed of information processing: results from a randomized, double-blind, placebo-controlled withdrawal study of seizure-free epilepsy patients receiving monotherapy. Epilepsia. 2006 Dec;47(12):2038-45.
- Lossius MI, et al. Consequences of antiepileptic drug withdrawal: a randomized, double-blind study (Akershus Study). Epilepsia. 2008 Mar;49(3):455-63. Epub 2007 Sep 19.
- D’Onofrio G, et al. Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med. 1999 Mar 25;340(12):915-9.
- Daeppen JB et al. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Arch Intern Med. 2002 May 27;162(10):1117-21.
- EO3 study. Ben-Menachem E et al. Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. First International Vagus Nerve Stimulation Study Group. Epilepsia. 1994 May-Jun;35(3):616-26.
- EO3 study. Ramsay RE et al. Vagus nerve stimulation for treatment of partial seizures: 2. Safety, side effects, and tolerability. First International Vagus Nerve Stimulation Study Group. Epilepsia. 1994 May-Jun;35(3):627-36.
- EO3 study. George R et al. Vagus nerve stimulation for treatment of partial seizures: 3. Long-term follow-up on first 67 patients exiting a controlled study. First International Vagus Nerve Stimulation Study Group. Epilepsia. 1994 May-Jun;35(3):637-43.
- Handforth A et al. Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology. 1998 Jul;51(1):48-55.
- Neal EG et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 2008 Jun;7(6):500-6. doi: 10.1016/S1474-4422(08)70092-9. Epub 2008 May 2.
- Trinka E et al; KOMET Study Group. KOMET: an unblinded, randomised, two parallel-group, stratified trial comparing the effectiveness of levetiracetam with controlled-release carbamazepine and extended-release sodium valproate as monotherapy in patients with newly diagnosed epilepsy. J Neurol Neurosurg Psychiatry. 2013 Oct;84(10):1138-47. doi: 10.1136/jnnp-2011-300376. Epub 2012 Aug 29.
- Marson AG, et al; SANAD Study group. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007 Mar 24;369(9566):1016-26.
- Marson AG et al; SANAD Study group. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007 Mar 24;369(9566):1000-15.
Last modified: December 10, 2015