Clinical Trial Results:
Theophylline Effect in Acute Ischemic Stroke Trial
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Summary
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EudraCT number |
2013-001989-42 |
Trial protocol |
DK |
Global end of trial date |
12 Mar 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Oct 2020
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First version publication date |
02 Oct 2020
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
TEA-Stroke
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Aalborg University Hospital
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Sponsor organisation address |
Mølleparkvej 4, Aalborg, Denmark, 9000
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Public contact |
TEA-Stroke Information Desk, Aalborg University Hospital, 45 97 66 22 71, aalborguh@rn.dk
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Scientific contact |
TEA-Stroke Information Desk, Aalborg University Hospital, 45 97 66 22 71, aalborguh@rn.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Dec 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 Mar 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Mar 2018
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
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
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Protection of trial subjects |
Possibility to withdraw informed consent.
GCP-monitoring of adverse events and laboratory parameters
Independent data safety monitoring board
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Background therapy |
Thrombolytic therapy with 0.9mg/kg alteplase and mechanical thrombectomy efter institutional standard of care and national guidelines for acute stroke treatment | ||
Evidence for comparator |
Theophylline | ||
Actual start date of recruitment |
08 Sep 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 64
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Worldwide total number of subjects |
64
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EEA total number of subjects |
64
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
23
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From 65 to 84 years |
39
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85 years and over |
2
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Recruitment
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Recruitment details |
1573 patients were treated with thrombolysis at the 2recruiting sites, 1216 patients were screened for the TEA-Stroke Trial by an investigator, 64 patients were finally randomized to the trial . | |||||||||
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Pre-assignment
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Screening details |
1216 patients were screened, 67 patients were enrolled, 3 patients did not fulfilled the MRI inclusion criteria, 64 were finally randomized to the trial | |||||||||
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Period 1
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Period 1 title |
overall period
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||
Blinding implementation details |
Web-based randomization
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Theophylline | |||||||||
Arm description |
10 mL of theophylline (Teofylamin 22 mg/mL containing 20 mg of theophylline monohydrate and 5.5 mg of solubilized ethylene-diamine hydrate) | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Theophylline
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Teofylamin 22 mg/mL containing 20 mg of theophylline monohydrate and 5.5 mg of solubilized ethylene-diamine hydrate as short intravenous infusion over 15 minutes
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Arm title
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Placebo | |||||||||
Arm description |
10 mL of physiological saline solution | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
physiological saline solution
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
10 mL of physiological saline solution as short intravenous infusion over 15 minutes
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Baseline characteristics reporting groups
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Reporting group title |
Theophylline
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Reporting group description |
10 mL of theophylline (Teofylamin 22 mg/mL containing 20 mg of theophylline monohydrate and 5.5 mg of solubilized ethylene-diamine hydrate) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
10 mL of physiological saline solution | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Theophylline
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Reporting group description |
10 mL of theophylline (Teofylamin 22 mg/mL containing 20 mg of theophylline monohydrate and 5.5 mg of solubilized ethylene-diamine hydrate) | ||
Reporting group title |
Placebo
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Reporting group description |
10 mL of physiological saline solution | ||
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End point title |
Early clinical improvement | ||||||||||||
End point description |
Change in NIHSS from baseline to 24 hour follow-up
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End point type |
Primary
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End point timeframe |
24 hour follow-up
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Statistical analysis title |
primary endpoint | ||||||||||||
Comparison groups |
Theophylline v Placebo
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Number of subjects included in analysis |
64
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Analysis specification |
Post-hoc
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.025 [1] | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
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upper limit |
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Variability estimate |
Standard deviation
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| Notes [1] - After correction for multiplicity (Bonferroni technique) |
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End point title |
Proportion of infarct growth | ||||||||||||
End point description |
Infarct growth at 24-hour follow-up was defined by the proportion of co-registered DWI lesion at 24-hour follow-up not present at baseline [(DWI follow-up–DWI baseline)/DWI baseline×100%]
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End point type |
Other pre-specified
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End point timeframe |
24 hour follow-up
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| Notes [2] - MRI follow-up at 24 h was not possible in 1 patient |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
3 month
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Theophylline
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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28 Jan 2015 |
Change of inclusion criterion NIHSS ≥ 6 to NIHSS ≥ 4:
The inclusion criterion NIHSS was lowered from 6 to 4 the majority of patients have less severe stroke and the severe stroke patients often are not able to give informed consent. The National Institute of Health Stroke Scale (NIHSS) measures the severity of stroke (NIHSS 0-4 corresponds to mild stroke symptoms, NIHSS 5-15 to moderate, NIHSS 16-20 to moderate to severe, and NIHSS ≥ 20 corresponds to severe stroke).
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24 Feb 2016 |
Change of method to assess the inclusion criteria perfusion/diffusion mismatch:
In the TEA-Stroke protocol, a semi-automatic in-house software was chosen to assess the MRI perfusion/diffusion-mismatch. Unfortunately, several potential trial candidates were excluded, as the semi-automatic calculation was not possible in time for technical reasons. The visual assessment of the perfusion/diffusion-mismatch based on the MRI-scanner software was allowed, if the semi-automatic calculation might not be available in time.
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20 Jun 2016 |
Change of inclusion criteria and extension of study period:
The delayed start of recruitment and the unexpected low recruitment rate made it necessary to extend the trial period to 1st February 2019, as the permission for the TEA-Stroke study will finish the 31th August 2016. The technical challenging and time consuming inclusion criterion “perfusion/diffusion-mismatch” was removed to improve the recruitment rate. Visit 2 at 2-3 hours after treatment with the trial medication was removed, as MRI was mainly performed at visit 2 to demonstrate the acute change of perfusion. An interim analysis was scheduled after inclusion of 60 patients
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| None reported | |||||||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/31008285 |
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