Lead Investigator: James Brorson, The University of Chicago
Title of Proposal Research: Examination of survivor functions from SOCRATES and THALES trials for kinetics of stroke recurrence
Vivli Data Request: 6550
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Study Summary for Lay Audience:
Stroke is a common and often devastating condition in which blockage of blood flow to a part of the brain leads to its destruction, with corresponding loss of function, producing a variety of symptoms such as paralysis of limbs or face, loss of speaking or comprehension, loss of peripheral vision, or loss of coordination and balance. Stroke is the leading cause of long-term disability in many societies, as well as a frequent reason for death. In the United States, some 800,000 persons suffer strokes each year, and over 100,000 die.
After an initial mild stroke, patients are at increased risk of having a second stroke. Such a recurrence can be devastating, producing severe disability. A number of clinical trials have tested medical treatments aimed at preventing these secondary strokes, and in testing these effects, have followed groups of stroke patients closely from the time of enrollment soon after the first stroke through 1 to 3 months following the stroke. Careful examination of the time course of outcomes in these groups of patients for the timing and rates of stroke recurrence can give us insight into the underlying conditions and states of patients following initial stroke. Such insights may help us devise better ways to prevent these recurrent strokes. The requested data from two recent stroke treatment trials has not been examined with this kind of kinetic analysis, and doing so will provide information about whether the timing of stroke recurrence is similar across different trials, pointing to shared underlying conditions.
The research proposed here will consist of quantitative analysis of the rates of events occurring in the subjects of the trials, both those in control groups and those in the active treatment groups. Survivor functions, representing the proportion of study subjects remaining free of an outcome event, will be estimated with a standard method called the Kaplan-Meier method. A mathematical formula derived from a theoretical kinetic model of the condition of the patients following stroke will be fitted to the observed survivor functions by adjustments of parameters in this model, using a standard mathematical approach called non-linear regression. The resulting values of the adjusted parameters will provide estimates of the kinetic rates affecting stroke recurrence in patients following initial stroke.
Study Rationale (Technical language):
Following incident stroke, stroke recurrence is front-loaded, perhaps indicating short-lived conditions of the blood vessels, heart, or brain that confer risk of recurrence of stroke. Kinetic modeling of stroke recurrence may provide insight into the number and duration of such states. Detection of short-lived states requires data on early recurrence, soon after the index event. Trials like Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT), Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE), Acute Stroke Or Transient IsChaemic Attack TReated With Aspirin or Ticagrelor and Patient OutcomES (SOCRATES) and Acute STroke or Transient IscHaemic Attack Treated With TicAgreLor and ASA for PrEvention of Stroke and Death (THALES), that enrolled and treated acute ischemic stroke or transient ischemic attack (TIA) patients in the early hours following index event occurrence, provide an accurate source of such information regarding the timing of recurrence of stroke after an initial TIA or minor stroke. Both control groups and groups treated with the active intervention can illuminate these kinetic features. We have chosen methods of quantitative analysis of this existing data to provide testing of the kinetic model’s mathematical predictions of survivor functions, and to determine the underlying kinetic parameters, as a direct approach to testing this theory of kinetic modeling.
Data Contributor: AstraZeneca
Study ID: NCT01994720
Sponsor ID: NCT01994720
Data Contributor: AstraZeneca
Study ID: NCT03354429
Sponsor ID: NCT03354429