Seizure Prophylaxis in Glioma (SPRING): A phase III randomised trial comparing prophylactic Levetiracetam versus no prophylactic anti-epileptic drug in  newly diagnosed presumed supratentorial glioma.


Session type:


Robin Grant1,Colin Watts2,Michael Jenkinson3,Luke Vale4,Tony Marson5,Robert Hill6,Tracy McEleny6
1NHS Lothian,2Department of Neurosurgery, University of Birmingham,3Department of Neurosurgery, Institute of Translational Medicine, University of Liverpool,4Institute of Health & Society Newcastle University Baddiley-Clark Building Richardson Road Newcastle upon Tyne,5Department of Neurology, Molecular and Clinical Pharmacology The Walton Centre NHS Foundation Trust University of Liverpool,6Scottish Clinical Trials Research Unit NHS National Services Scotland Gyle Square 1 South Gyle Crescent Edinburgh



There is no consensus regarding the need for prophylactic anti-epileptic drug (AED) in newly-diagnosed suspected glioma patients who have not experienced seizures. Data regarding prophylactic AED use is scant and inconclusive. Most of the available evidence comes from older, small studies that enrolled patients with brain metastases and benign tumours in addition to gliomas. A definitive randomised clinical trial is needed to determine whether the policy of prophylactic AED therapy reduces the risk of first seizures in this patient population.


SPRING is a two arm, multicentre, phase III RCT of prophylactic AED (Levetiracetam) versus no AED (comparator) in patients with suspected cerebral glioma. 

Primary Outcome is one year risk of first seizure. Secondary outcomes include: time to first seizure, time to first tonic-clonic seizure, mood, personality, fatigue and memory and quality of life. Secondary tumour outcomes include: progression free survival and overall survival and incremental cost per QALY.

Patients are randomised 1:1. Levetiracetam will be given at 500mg twice daily for 2 weeks, then increasing to 750mg twice daily thereafter for 1 year. This will not be a blinded study and will not have placebo control. Inclusion criteria includes suspected cerebral glioma on CT/MRI, Capable of giving informed consent, age ≥ 16 years old and Karnofsky performance status of > 60.

Estimate of 1 year seizure rate in patients with suspected glioma after surgery is 20%. Based on a reduction in seizure rate to 10% in the treatment arm, a total of 806 patients will be required. 



The trial is in the set up stage and 15 Neuroscience centres will be recruited with planned first enrolment in Jan 2019.  The study will recruit for 3 years.


SPRING will be the largest RCT in neuro-oncology, and will include nearly twice as many patients as the previous five RCTs combined.