Clinical Trials

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!
If you think something should be added or corrected, please let us know!
 


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:

  1. Saver JL, et al SWIFT Trialists. Lancet. 2012 Oct 6;380(9849):1241-9.
  2. 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:

  1. Furlan A, et al PROACT II. JAMA. 1999 Dec 1;282(21):2003-11.
  2. Broderick JP, et al, IMS III. N Engl J Med. 2013 Mar 7;368(10):893-903.
  3. Kidwell CS, et al MR RESCUE. N Engl J Med. 2013 Mar 7;368(10):914-23.
  4. 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:

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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