Acute ischemic stroke patients eligible for standard intravenous recombinant tissue plasminogen activator (rtPA) thrombolytic therapy with magnet resonance imaging (MRI)-proved infarction MedDRA version: 19.0 Level: LLT Classification code 10023027 Term: Ischaemic stroke NOS System Organ Class: 100000004852
Conditions
Interventions
Product Name: Teofylamin 22mg/ml
Product Code: 88013322012
Pharmaceutical Form: Infusion
INN or Proposed INN: THEOPHYLLINE MONOHYDRATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration t
Sponsors
Boris Modrau
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Subjects eligible for standard dose IV rtPA thrombolytic therapy within 4.5 hours of symptom onset in accordance to the national Danish inclusion /exclusion criteria for standard IV rtPA thrombolytic therapy •Patients with acute hemispheric cerebral infarction as defined by DWI. •National Institute of Health Stroke Scale (NIHSS) =4 •DWI lesion volume =1/3 of MCA territory or =1/2 of ACA or PCA territory •Informed consent obtained. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: •Age below 18 years •Pre-stroke disability defined by modified Rankin Scale (mRS) >1 •Contraindication to MRI •Acute infarction of the brainstem on diffusion weighted MRI at baseline •Occlusion of the internal carotid artery or carotid-T on MRI at baseline •Epilepsy and/or acute seizure •Treatment with or allergic reaction to xanthines (Teofylin or its derivates) •Pregnancy, breastfeeding, or positive pregnancy test (Negative pregnancy test prior to Teofylin administration required in fertile women up to 55 years of age) •History of liver disease and/or alanine transaminase two times normal value •History of thyroidal dysfunction •Fever of more than 38.5 °C •Potassium below normal value •Electrocardiogram with signs of acute ischemic heart disease •Congestive heart failure, or acute myocardial infarction within the last 6 months •Reduced cooperation or other conditions that make it unlikely to precede the study or to follow the patient for three months •Participation in any interventional study within the last 30 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this study is to evaluate safety and efficacy of add-on Teofylin treatment to standard thrombolytic therapy in patients with MR-proved acute ischemic stroke. The study is designed as a randomized controlled trial comparing add-on Teofylin to placebo. The main interests are to demonstrate the tissue effect of Teofylin by measuring the infarct growth assessed by multimodal MRI as well as improved early clinical outcome;Secondary Objective: Not applicable;Primary end point(s): Dual Primary Outcome Measures •Infact growth at 22-32 hours after add-on Teofylin treatment •Clinical improvement at 22-32 hours after add-on Teofylin treatment;Timepoint(s) of evaluation of this end point: 22-32 hours after add-on Teofylin treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Major clinical improvement 22-32 hours after add-on Teofylin treatment: Major clinical improvement is defined by =50% improvement in the NIHSS. •Recanalization rate from baseline to 22-32 hours after add-on Teofylin treatment: The recanalization rate is defined as change of the thrombolysis in myocardial infarction (TIMI) score 0 or 1 at baseline to TIMI at 22-32 hours. •Dichotomized favourable functional outcome: Dichotomized functional outcome at day 90±14 defined by the modified Rankin scale (mRS), which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death: The secondary endpoint is dichotomized as favourable functional outcome (mRS score of 0 or 1) or unfavourable functional outcome (mRS score of 2 to 6). •Categorical shift in functional outcome: Functional outcome measures with the categorical shift (ordinal analysis) of the mRS at day 90±14. •A subgroup analysis for the primary and secondary endpoints will be performed for subjects with and without persistent symptomatic vessel occlusion, for subjects with non-lacunar infarction, and for subjects with endovascular therapy IV rtPA treatment (bridging theray). Subjects recruited in accordance to the TEA-Stroke protocol version 4.2 will be analysed per protocol version 4.2 for all endpoints as substudy analysis Safety Outcome Measures •Death within 90±14 days •Parenchyma hematoma type I or II (PH-1 or PH-2) at 22-32 hours on brain imaging •Symptomatic intracerebral haemorrhage (ICH) as a combined clinical/imaging endpoint defined by parenchyma hematoma type II (PH-2) on brain imaging and a clinical assessment with a decline =4 on NIHSS or death. ;Timepoint(s) of evaluation of this end point: 22-32 hours, and day 90±14 after add-on Teofylin treatment | — |
Countries
Denmark
Contacts
Public ContactTEA-Stroke Information Desk
Aalborg University Hospital
Outcome results
None listed