Therapy
Thrombolysis during Resuscitation
This review may be edited
Summary
Posted By: jon field
E-Mail: jonathan_field@health.qld.gov.au
Posted Date: 5/3/9
Title: Thrombolysis during Resuscitation
Authors: Bernd W. Böttiger
Reference: N Engl J Med 2008;359:2651-62.
Link: Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract: BACKGROUND Approximately 70% of persons who have an out-of-hospital cardiac arrest have underlying acute myocardial infarction or pulmonary embolism. Therefore, thrombolysis during cardiopulmonary resuscitation may improve survival.
METHODS In a double-blind, multicenter trial, we randomly assigned adult patients with witnessed out-of-hospital cardiac arrest to receive tenecteplase or placebo during cardiopulmonary resuscitation. Adjunctive heparin or aspirin was not used. The primary end point was 30-day survival; the secondary end points were hospital admission, return of spontaneous circulation, 24-hour survival, survival to hospital discharge, and neurologic outcome.
RESULTS After blinded review of data from the first 443 patients, the data and safety monitoring board recommended discontinuation of enrollment of asystolic patients because of low survival, and the protocol was amended. Subsequently, the trial was terminated prematurely for futility after enrolling a total of 1050 patients. Tenecteplase was administered to 525 patients and placebo to 525 patients; the two treatment groups had similar clinical profiles. We did not detect any significant differences between tenecteplase and placebo in the primary end point of 30-day survival (14.7% vs. 17.0%; P = 0.36; relative risk, 0.87; 95% confidence interval, 0.65 to 1.15) or in the secondary end points of hospital admission (53.5% vs. 55.0%, P = 0.67), return of spontaneous circulation (55.0% vs. 54.6%, P = 0.96), 24-hour survival (30.6% vs. 33.3%, P = 0.39), survival to hospital discharge (15.1% vs. 17.5%, P = 0.33), or neurologic outcome (P = 0.69). There were more intracranial hemorrhages in the tenecteplase group.
CONCLUSIONS When tenecteplase was used without adjunctive antithrombotic therapy during advanced life support for out-of-hospital cardiac arrest, we did not detect an improvement in outcome, in comparison with placebo. (ClinicalTrials.gov number, NCT00157261.)
 
Are the Results Valid?
1. Was the assignment of patients to treatments randomized? ( Was allocation concealment maintained?)
The treatment assignments of study drugs were randomly generated and stratified according to individual mobile ICU in blocks of four.
The authors do not explicitly state how allocation concealment was maintained (unlear).
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
complete follow up was available for 1032 out of 1050 pts.
Survival data was available for 1043 pts. and the remaining 7 were assumed dead
2b. Were patients analyzed in the groups to which they were randomized?
Yes.
Fifty-eight patients (29 assigned to tenecteplase and 29 assigned to placebo) did not receive the study drug; in 33 of these 58 patients (18 assigned to receive tenecteplase and 15 assigned to receive placebo), the return of spontaneous circulation had already occurred; in 19 (8 and 11, respectively),exclusion criteria were detected after randomization; and in 6 (3 and 3, respectively), the study drug was not administered for other, miscellaneous reasons.
It appears the analysis included these patients in theire respective groups.
3. Were patients, health workers, and study personnel blind to treatment?
Yes. This trial was placebo-blinded
4. Were the groups similar at the start of the trial?
Table 1 and 2 show good balance. Table 3 shows there was imbalance in the Presumed cause of cardiac arrest, perhaps due to a higher incidence of myocardial infaction in the thrombolysis group 75% vs. 68.5%.
5. Aside from the experimental intervention, were the groups treated equally?
Basic life support, defib and drugs given prehosp were similar. PCI and CABG rates were similiar. Therapeutic hypothermia was more frequently used in the placebo group 56% than lysis group 47%.
What are the Results?
1. How large was the treatment effect?
After blinded review of data from the first 443 patients, the data and safety monitoring board recommended discontinuation of enrollment of asystolic patients because of low survival, and the protocol was amended.
Subsequently, the trial was terminated prematurely for futility after enrolling a total of 1050 patients.
Tenecteplase was administered to 525 patients and placebo to 525 patients;
there were no differences between the 2 groups in the primary end point of 30-day survival
  • 14.7% vs. 17.0%; P = 0.36; relative risk, 0.87; 95% confidence interval, 0.65 to 1.15 or
    in the secondary end points of:
    hospital admission
  • 53.5% vs. 55.0%, P = 0.67,
    return of spontaneous circulation
  • 55.0% vs. 54.6%, P = 0.96,
    24-hour survival
  • 30.6% vs. 33.3%, P = 0.39,
    survival to hospital discharge
  • 15.1% vs. 17.5%, P = 0.33, or
    neurologic outcome
  • P = 0.69.
    There were more intracranial hemorrhages in the tenecteplase group.
  • 2. How precise was the estimate of the treatment effect?
    See above.
    Will the Results Help Me In Caring For My Patients?
    1. Can the results be applied to my patient care?
    30 such patients a year are admitted to our unit
    2. Were all clinically important outcomes considered?
    Yes. survival and haemorrhage were studied
    3. Are the likely treatment benefits worth the potential harms and costs?
    No. There were no documented treatment benefits and there were 4 systomoatic intracranial bleeds in the lysis group and none in the placebo.

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