JC Idarucizumab

7/24/2019 JC Idarucizumab

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Journal Club

Idarucizumab for Dabigatran Reversal

.

533150189-6 6


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REVERSE-AD

Reversal Effects of Idarucizumab on

Active Dabigatran

Impact factor = 55.873 (2014)


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Outline

Background and Rationale

Objective

Methods

Results

Conclusion

Critical Appraisal Skills Programme (CASP)


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CRITICAL APPRAISAL SKILLS

PROGRAMME

Checklist for cohort studies

Are the results of the study valid? What are the results?

Will the results help locally?


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(A)1. Did the study address a clearly

focused issue?

Yes, the study clearly focuses on beneficial

effect as the efficacy and safety of

idarucizumab as reversal agent fordabigatran.


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Background and Rationale

Specific reversal agents for non-vitamin K

antagonists oral anticoagulants are lacking.

Idarucizumab is developed to reverse its

effects.


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Objective

Demonstrate efficacy of idarucizumab for reversal of

anticoagulant effect of Dabigatran

Assessment of bleeding and safety of idarucizumab


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(A) 2. Was the cohort recruited in an

acceptable way?

Yes

Cohort is a representative of defined

population.However, this study only included the

bleeding patients whose dilute thrombin

time and ecarin clotting time above the

upper limit of normal range.


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Methods

Multicenter study (>400 centers in 38

countries)

Open label, uncontrolled, prospective cohort

study

Interim study

Clinical study Phase 3


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Study Eligibility

Inclusion criteria

Adults, 18 years or older, taking dabigatran

Presented in Emergency department

Exclusion criteria

Patients whose have dTT and ECT above

upper limit of normal range.


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Study Design

Group APatients who exhibit sign and

symptoms of uncontrolled or

life-threatening bleeding

Group BPatients who require emergency

surgery /other medical procedure

necessitating rapid reversal of

anticoagulant effect of dabigatran

before surgery/ procedure

Patients received 5g of IV idarucizumab as

two 50ml bolus infusions, administered15 minutes apart


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3. Was the exposure accurately

measured to minimize bias?

Yes

Efficacy of Idarucizumab is measured using

dilute thrombin time and ecarin clotting

time which is an objective measures.

All the subjects classified into eachexposure group using the same procedure.


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Study Endpoints

Primary endpoint- maximum percentage of

reversal of anticoagulant effect of dabigatran

(measured by dilute thrombin time or ecarin

clotting time)

Secondary endpoint-

Proportion of patients who had complete

normalization of the dilute thrombin time or

ecarin clotting time in the first 4 hours and thereduction in the concentration of unbound

dabigatranClinical outcomes as assessed by the physicians


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4. Was the outcome accurately

measured to minimize bias?

Yes,

Similar measurement methods in the

different groups.Use of ECT and dTT comes from results of

previous study (Glund et al.)

No blinding is done.


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Statistical Analysis

Descriptive statistics with Confidence

interval or percentile as appropriate


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5. (a) Have the authors identified all important

confounding factors?

(b) Have they taken account of the confoundingfactors in the design and/or analysis?

Cant tell

No confounding factor is noted inthis study.


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6. Was the follow up of subjects

complete and long enough?

Yes,

After receiving Idarucizumab,patients were followed until death or

for at least 1 month.


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(B) 7. What are the results of this study?

8. How precise are the results?

Median maximum percentage reversal in the

patients in group A and B were 100%( 95%CI 100 to 100), evident after 1stinfusion.


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Results


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Results


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Results


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Results


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Results


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9. Do you believe the results?

Cant tell,Number of patients is too small (total of 90 patients)

More number of patients are needed in the study.

(C) 10. Can the results be applied to the localpopulation?

Yes,

It would be unethical to use RCT in these

patients.The results can be generalized.


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11. Do the results of this study fit with

other available evidence?

Yes,

It is consistent with the previous studyperformed in healthy volunteers.

12. What are the implications of this study for

practice?

This interim study provides the result tosupport that idarucizumab can be used to

reverse the anticoagulant effects ofdabigatran.


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Conclusion

Idarucizumab rapidly and completely

reversed the anticoagulant activity of

dabigatran in 88 to 98% of patients.No safety concerns


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Reference

1. Pollack CV, Reilly PA, Eikelboom J, Glund S,

Verhamme P, Bernstein R, et al. Idarucizumab

for Dabigatran Reversal. N Engl J Med2015;373:511-20

2. Critical Apprasial Skills Programme, cohortstudy checklist (2013)

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