Trial Outcomes & Findings for Activated Protein C in Acute Stroke Trial (NCT NCT00533546)

Last Updated: 2016-10-24

Results Overview

Intracranial Hemorrhage (ICH): Fatal ICH: Death ascribed to ICH confirmed by autopsy or CT imaging. Major non-fatal ICH: Hemorrhage within brain parenchyma associated with neurological deterioration or evidence of subdural, epidural or intraventricular hemorrhage on CT imaging, with or without symptoms. Symptomatic ICH: Hemorrhage within the territory of qualifying infarction with neurological deterioration as measured by \> 2 point increase in the National Institutes of Health Stroke Scale (NIHSS) from previous examination; hemorrhage in different vascular territory associated with new neurologic deficit. All symptomatic ICH will be defined as a major ICH. Asymptomatic ICH: Presence of hemorrhage within the territory of qualifying infarction without neurological deterioration ascribed to the hemorrhage or presence of hemorrhage within brain parenchyma outside the territory of qualifying infarction without new neurologic deficit (would not be considered a major ICH)

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Measured within 36-48 hours of treatment

Results posted on

2016-10-24

Participant Flow

The recruitment period spanned the following dates: October 2007 through July 2010. Location of recruitment and enrollment was in the emergency department of approved sites for patients presenting with acute ischemic stroke. Of the 9 participating sites, 3 actively enrolled.

No patients were excluded after enrollment.

Participant milestones

Participant milestones
Measure	Intravenous APC 10 Microgram/kg Dose Participants will receive APC by intravenous injection, receiving 50% of dose as a bolus and the remainder as an infusion over one hour. Activated Protein C : Intravenous APC (10 mcg/kg) administered to patients with acute ischemic stroke within 0 - 9 hours of symptom onset
Overall Study STARTED	12
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Activated Protein C in Acute Stroke Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intravenous APC 10 Microgram/kg Dose n=12 Participants Participants will receive APC by intravenous injection, receiving 50% of dose as a bolus and the remainder as an infusion over one hour. Activated Protein C : Intravenous APC (10, 15, 22, 33, 50, and 75 mcg/kg) administered to patients with acute ischemic stroke within 0 - 9 hours of symptom onset
Age, Continuous	71.6 years STANDARD_DEVIATION 17.3 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants

PRIMARY outcome

Timeframe: Measured within 36-48 hours of treatment

Population: All participants enrolled were analyzed.

Outcome measures

Outcome measures
Measure	Intravenous APC 10 Microgram/kg Dose n=12 Participants Participants will receive APC by intravenous injection, receiving 50% of dose as a bolus and the remainder as an infusion over one hour. Activated Protein C : Intravenous APC (10, 15, 22, 33, 50, and 75 mcg/kg) administered to patients with acute ischemic stroke within 0 - 9 hours of symptom onset
Number of Participants With Intracranial Hemorrhage	0 participants

SECONDARY outcome

Timeframe: 90 days

Measure of disability as determined by categorical assignment on modified Rankin Scale.. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms. 1. \- No significant disability. Able to carry out all usual activities, despite some symptoms. 2. \- Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3. \- Moderate disability. Requires some help, but able to walk unassisted. 4. \- Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5. \- Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6. \- Dead.

Outcome measures

Outcome measures
Measure	Intravenous APC 10 Microgram/kg Dose n=12 Participants Participants will receive APC by intravenous injection, receiving 50% of dose as a bolus and the remainder as an infusion over one hour. Activated Protein C : Intravenous APC (10, 15, 22, 33, 50, and 75 mcg/kg) administered to patients with acute ischemic stroke within 0 - 9 hours of symptom onset
Mean Modified Rankin Scale Score	2.91 units on a scale Standard Deviation 1.58

SECONDARY outcome

Timeframe: 90 days

Measure of functional recovery using Barthel Index (range 0-100). The Barthel scale or Barthel ADL index is an ordinal scale used to measure performance in activities of daily living (ADL). Each performance item is rated on this scale with a given number of points assigned to each level or ranking. It uses ten variables describing ADL and mobility with 10 points given to each variable for a total of 100 points. A higher number is associated with a greater likelihood of being able to live at home with a degree of independence following discharge from hospital. The ten variables addressed in the Barthel scale are: presence or absence of fecal incontinence presence or absence of urinary incontinence help needed with grooming help needed with toilet use help needed with feeding help needed with transfers (e.g. from chair to bed) help needed with walking help needed with dressing help needed with climbing stairs and help needed with bathing

Outcome measures

Outcome measures
Measure	Intravenous APC 10 Microgram/kg Dose n=12 Participants Participants will receive APC by intravenous injection, receiving 50% of dose as a bolus and the remainder as an infusion over one hour. Activated Protein C : Intravenous APC (10, 15, 22, 33, 50, and 75 mcg/kg) administered to patients with acute ischemic stroke within 0 - 9 hours of symptom onset
Mean Barthel Index Score	67.7 units on a scale Standard Deviation 34.2

SECONDARY outcome

Timeframe: 90 days

The NIHSS is a measure of neurologic deficit on a scale of 0-42, with 0 being normal. The National Institutes of Health Stroke Scale, or NIH Stroke Scale (NIHSS) is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0. The 11 items are: Level of Consciousness Horizontal Eye Movement Visual field test Facial Palsy Motor Arm Motor Leg Limb Ataxia Sensory Language Speech Extinction and Inattention

Outcome measures

Outcome measures
Measure	Intravenous APC 10 Microgram/kg Dose n=12 Participants Participants will receive APC by intravenous injection, receiving 50% of dose as a bolus and the remainder as an infusion over one hour. Activated Protein C : Intravenous APC (10, 15, 22, 33, 50, and 75 mcg/kg) administered to patients with acute ischemic stroke within 0 - 9 hours of symptom onset
National Institutes of Health Stroke Scale (NIHSS)	5.0 units on a scale Standard Deviation 4.2

Adverse Events

Intravenous APC 10 Microgram/kg Dose

Serious events: 5 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Intravenous APC 10 Microgram/kg Dose n=12 participants at risk Participants will receive APC by intravenous injection, receiving 50% of dose as a bolus and the remainder as an infusion over one hour. Activated Protein C : Intravenous APC (10, 15, 22, 33, 50, and 75 mcg/kg) administered to patients with acute ischemic stroke within 0 - 9 hours of symptom onset
Nervous system disorders worsening of neurological symptoms	25.0% 3/12 • Number of events 5 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
General disorders Hospitalization > 24 hours	25.0% 3/12 • Number of events 3 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
General disorders death	8.3% 1/12 • Number of events 1 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.

Other adverse events

Other adverse events
Measure	Intravenous APC 10 Microgram/kg Dose n=12 participants at risk Participants will receive APC by intravenous injection, receiving 50% of dose as a bolus and the remainder as an infusion over one hour. Activated Protein C : Intravenous APC (10, 15, 22, 33, 50, and 75 mcg/kg) administered to patients with acute ischemic stroke within 0 - 9 hours of symptom onset
Blood and lymphatic system disorders Anaemia	25.0% 3/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Blood and lymphatic system disorders Leukocytosis	25.0% 3/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Cardiac disorders Acute myocardial infarction	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Cardiac disorders Cardiac failure congestive	16.7% 2/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Cardiac disorders Cardiomegaly	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Cardiac disorders Oedema peripheral	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Cardiac disorders Tachycardia	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Congenital, familial and genetic disorders Atrial septal defect	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Endocrine disorders Hypoglycaemia	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Endocrine disorders Hypothyroidism	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Eye disorders Eye discharge	16.7% 2/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Gastrointestinal disorders Abdominal pain	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Gastrointestinal disorders Constipation	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Gastrointestinal disorders Diarrhoea	16.7% 2/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Gastrointestinal disorders Gastrointestinal haemorrhage	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Gastrointestinal disorders Haematemesis	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Gastrointestinal disorders Nausea	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Gastrointestinal disorders Oral candidiasis	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Gastrointestinal disorders Oral fungal infection	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Gastrointestinal disorders Vomiting	16.7% 2/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
General disorders Catheter site pain	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
General disorders Discomfort	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
General disorders Implant site pain	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
General disorders Lethargy	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
General disorders Pain	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
General disorders Pyrexia	50.0% 6/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Infections and infestations Cellulitis	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Infections and infestations Enterococcal infection	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Infections and infestations Sepsis	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Infections and infestations Tinea pedis	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Infections and infestations Urinary tract infection	58.3% 7/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Injury, poisoning and procedural complications Contusion	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Injury, poisoning and procedural complications Fall	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Injury, poisoning and procedural complications Infusion related reaction	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Injury, poisoning and procedural complications Renal injury	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Injury, poisoning and procedural complications Skin laceration	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Investigations Blood cholesterol increased	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Investigations Body temperature increased	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Investigations Electrocardiogram change	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Investigations Neurological examination abnormal	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Investigations Vibration test abnormal	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Investigations White blood cell count increased	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Metabolism and nutrition disorders Hyperkalaemia	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Metabolism and nutrition disorders Hyperlipidaemia	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Metabolism and nutrition disorders Hypocalcaemia	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Metabolism and nutrition disorders Hypokalaemia	25.0% 3/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Metabolism and nutrition disorders Hyponatraemia	25.0% 3/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Metabolism and nutrition disorders Ketoacidosis	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Metabolism and nutrition disorders Magnesium deficiency	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Musculoskeletal and connective tissue disorders Back pain	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Musculoskeletal and connective tissue disorders Contusion	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Musculoskeletal and connective tissue disorders Groin pain	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Musculoskeletal and connective tissue disorders Muscle twitching	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	25.0% 3/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Musculoskeletal and connective tissue disorders Neck pain	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Skin and subcutaneous tissue disorders Lipoma	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Nervous system disorders Brain oedema	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Nervous system disorders Disturbance in attention	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Nervous system disorders Headache	25.0% 3/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Nervous system disorders Insomnia	25.0% 3/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Nervous system disorders Muscle spasticity	25.0% 3/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Nervous system disorders Neurological symptom	16.7% 2/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Nervous system disorders Status epilepticus	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Psychiatric disorders Agitation	16.7% 2/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Psychiatric disorders Anxiety	16.7% 2/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Psychiatric disorders Confusional state	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Psychiatric disorders Delirium	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Psychiatric disorders Depression	41.7% 5/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Psychiatric disorders Insomnia	25.0% 3/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Psychiatric disorders Suicidal ideation	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Renal and urinary disorders Haematuria	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Renal and urinary disorders Renal cyst	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Renal and urinary disorders Urinary retention	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Respiratory, thoracic and mediastinal disorders Atelectasis	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Respiratory, thoracic and mediastinal disorders Increased upper airway secretion	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Respiratory, thoracic and mediastinal disorders Pleural effusion	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Respiratory, thoracic and mediastinal disorders Pneumonia	16.7% 2/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Respiratory, thoracic and mediastinal disorders Respiratory distress	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Respiratory, thoracic and mediastinal disorders Small cell lung cancer stage unspecified	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Skin and subcutaneous tissue disorders Decubitus ulcer	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Skin and subcutaneous tissue disorders Petechiae	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Skin and subcutaneous tissue disorders Pruritus	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Skin and subcutaneous tissue disorders Rash	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Skin and subcutaneous tissue disorders Skin disorder	16.7% 2/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Skin and subcutaneous tissue disorders Urticaria	8.3% 1/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Surgical and medical procedures Gastrointestinal tube insertion	25.0% 3/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Vascular disorders Deep vein thrombosis	16.7% 2/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.
Vascular disorders Hypertension	16.7% 2/12 • 90 days following enrollment Serious Adverse Events were collected without regard to the specific Adverse Event Term.

Additional Information

Curtis Benesch, M.D., M.P.H.

University of Rochester

Phone: 585 275-2530

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place