Trial Outcomes & Findings for A Study of Intravenous Thrombolysis With Alteplase in MRI-Selected Patients (NCT NCT01282242)

NCT ID: NCT01282242

Last Updated: 2017-06-15

Results Overview

Safety of IV rt-PA as evident by rates of symptomatic ICH defined by an increase of 4 points or more on the NIHSS .

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

88 participants

Primary outcome timeframe

Within 7 days from tPA administration.

Results posted on

2017-06-15

Participant Flow

Subjects were recruited between January 2011 and February 2016 from 14 sites across the continental United States, and enrolled in 10 of those sites.

Subjects diagnosed with acute ischemic stroke, last known well within 24 hours of triage and able to receive IV rt-PA within 4.5 hours from symptom discovery based on MRI findings consistent with early stroke onset, were eligible. MRI Signal Intensity Ration values were defined as \<1.15 for the primary and \<1.25 for the secondary arm of the trial.

Participant milestones

Participant milestones
Measure	Primary SIR <1.15 MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) \<1.15 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)	Secondary SIR <1.25 MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) \<1.25 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)
Overall Study STARTED	80	8
Overall Study COMPLETED	80	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Intravenous Thrombolysis With Alteplase in MRI-Selected Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SIR <1.15 n=80 Participants MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) \<1.15 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)	SIR <1.25 n=8 Participants MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) \<1.25 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)	Total n=88 Participants Total of all reporting groups
Age, Continuous	67.46 years STANDARD_DEVIATION 13.5 • n=99 Participants	67.13 years STANDARD_DEVIATION 11.63 • n=107 Participants	67.43 years STANDARD_DEVIATION 13.26 • n=206 Participants
Sex: Female, Male Female	37 Participants n=99 Participants	4 Participants n=107 Participants	41 Participants n=206 Participants
Sex: Female, Male Male	43 Participants n=99 Participants	4 Participants n=107 Participants	47 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=99 Participants	0 Participants n=107 Participants	6 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	73 Participants n=99 Participants	8 Participants n=107 Participants	81 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Asian	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	28 Participants n=99 Participants	5 Participants n=107 Participants	33 Participants n=206 Participants
Race (NIH/OMB) White	47 Participants n=99 Participants	2 Participants n=107 Participants	49 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants
NIH Stroke Scale (NIHSS)	9.31 units on a scale STANDARD_DEVIATION 5.87 • n=99 Participants	10.13 units on a scale STANDARD_DEVIATION 4.64 • n=107 Participants	9.35 units on a scale STANDARD_DEVIATION 5.91 • n=206 Participants
Modified Rankin Scale	0.48 units on a scale STANDARD_DEVIATION 1.09 • n=99 Participants	1.38 units on a scale STANDARD_DEVIATION 2.26 • n=107 Participants	1.18 units on a scale STANDARD_DEVIATION 1.72 • n=206 Participants

PRIMARY outcome

Timeframe: Within 7 days from tPA administration.

Safety of IV rt-PA as evident by rates of symptomatic ICH defined by an increase of 4 points or more on the NIHSS .

Outcome measures

Outcome measures
Measure	SIR <1.15 n=80 Participants MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) \<1.15 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)	SIR < 1.25 n=8 Participants MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) \<1.25 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)
Number of Subjects With Symptomatic Intracerebral Hemorrhage	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Within 96 hours of tPA administration

Safety of IV rt-PA as evident by rates of symptomatic cerebral edema defined as brain edema with mass effect as the predominant cause of clinical deterioration.

Outcome measures

Outcome measures
Measure	SIR <1.15 n=80 Participants MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) \<1.15 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)	SIR < 1.25 n=8 Participants MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) \<1.25 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)
Number of Subjects With Symptomatic Cerebral Edema	3 Participants	0 Participants

Adverse Events

SIR <1.15

Serious events: 22 serious events

Other events: 56 other events

Deaths: 7 deaths

SIR <1.25

Serious events: 5 serious events

Other events: 8 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Lee H. Schwamm, MD

Massachusetts General Hospital

Phone: 617-724-1597

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	SIR <1.15 n=80 participants at risk MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) \<1.15 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)	SIR <1.25 n=8 participants at risk MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) \<1.25 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)
General disorders Asthenia	1.2% 1/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Cardiac disorders Atrial Fibrillation	3.8% 3/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Nervous system disorders Brain Oedema	7.5% 6/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Cardiac disorders Cardio-Respiratory Arrest	1.2% 1/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Nervous system disorders Cerebral Heamorrhage	2.5% 2/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Nervous system disorders Cerebrovascular Accident	3.8% 3/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Psychiatric disorders Confusional State	2.5% 2/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Nervous system disorders Convulsion	2.5% 2/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
General disorders Death	3.8% 3/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Gastrointestinal disorders Gastrointestinal Heamorrhage	1.2% 1/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Vascular disorders Heamatoma	1.2% 1/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Nervous system disorders Haemorrhage Intracranial	2.5% 2/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Metabolism and nutrition disorders Hyperkalaemia	1.2% 1/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Nervous system disorders Ischaemic Stroke	1.2% 1/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Psychiatric disorders Mental Status Changes	2.5% 2/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Nervous system disorders Neurological Symptom	1.2% 1/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Infections and infestations Pneumonia	1.2% 1/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Respiratory, thoracic and mediastinal disorders Pneumonia Aspiration	1.2% 1/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	1.2% 1/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	5.0% 4/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Infections and infestations Septic Shock	1.2% 1/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Gastrointestinal disorders Upper Gastrointestinal Haemorrhage	1.2% 1/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Vascular disorders ANGIOEDEMA	0.00% 0/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Nervous system disorders BRAIN HERNIATION	0.00% 0/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Vascular disorders CAROTID ARTERY STENOSIS	0.00% 0/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Injury, poisoning and procedural complications FALL	0.00% 0/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Vascular disorders MYOCARDIAL INFARCTION	0.00% 0/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.

Measure	SIR <1.15 n=80 participants at risk MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) \<1.15 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)	SIR <1.25 n=8 participants at risk MRI confirmed early stroke onset, determined by Signal intensity ratio (SIR) \<1.25 (SIR = Contralateral Region Of Interest (ROI)/Ipsilateral ROI)
Psychiatric disorders Agitation	5.0% 4/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Nervous system disorders Cerebral Haemorrhage	5.0% 4/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Gastrointestinal disorders Constipation	8.8% 7/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Psychiatric disorders Depression	5.0% 4/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Skin and subcutaneous tissue disorders Ecchymosis	6.2% 5/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Nervous system disorders Heamorrhagic Transformation	22.5% 18/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Nervous system disorders Headache	16.2% 13/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Gastrointestinal disorders Nausea	10.0% 8/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Skin and subcutaneous tissue disorders Petechiae	5.0% 4/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	25.0% 2/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
General disorders Pyrexia	10.0% 8/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Infections and infestations Urinary Tract Infection	15.0% 12/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Gastrointestinal disorders Vomiting	7.5% 6/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	0.00% 0/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Nervous system disorders Amnesia	0.00% 0/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Respiratory, thoracic and mediastinal disorders ATELECTASIS	0.00% 0/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Vascular disorders ATRIAL FIBRILLATION	0.00% 0/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
General disorders GINGIVAL BLEEDING	0.00% 0/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Injury, poisoning and procedural complications HEAD INJURY	0.00% 0/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Metabolism and nutrition disorders HYPOGLYCAEMIA	0.00% 0/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Skin and subcutaneous tissue disorders INJECTION SITE EXTRAVASATION	1.2% 1/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Injury, poisoning and procedural complications LIMB INJURY	0.00% 0/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	1.2% 1/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.
Musculoskeletal and connective tissue disorders OROPHARYNGEAL PAIN	0.00% 0/80 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.	12.5% 1/8 • Adverse events were collected from the time subjects were consented through study completion, a 90 day period, about 3 months.