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Journal Club

Idarucizumab for Dabigatran Reversal


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533150189-6 6

Impact factor = 55.873 (2014)

REVERSE-AD
Reversal Effects of Idarucizumab on
Active Dabigatran

Outline
Background and Rationale
Objective
Methods
Results
Conclusion
Critical Appraisal Skills Programme (CASP)

CRITICAL APPRAISAL SKILLS


PROGRAMME
Checklist for cohort studies
Are the results of the study valid?
What are the results?
Will the results help locally?

(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 for
dabigatran.

Background and Rationale


Specific reversal agents for non-vitamin K
antagonists oral anticoagulants are lacking.
Idarucizumab is developed to reverse its
effects.

Objective
Demonstrate efficacy of idarucizumab for reversal of
anticoagulant effect of Dabigatran
Assessment of bleeding and safety of idarucizumab

(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.

Methods
Multicenter study (>400 centers in 38
countries)
Open label, uncontrolled, prospective cohort
study
Interim study
Clinical study Phase 3

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.

Study Design
Group A

Patients who exhibit sign and


symptoms of uncontrolled or
life-threatening bleeding

Group B

Patients 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, administered
15 minutes apart

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 each
exposure group using the same procedure.

Study Endpoints
Primary endpoint- maximum percentage of
reversal of anticoagulant effect of dabigatran
(measured by dilute thrombin time or ecarin
clotting time)
Secondary endpointProportion of patients who had complete
normalization of the dilute thrombin time or
ecarin clotting time in the first 4 hours and the
reduction in the concentration of unbound
dabigatran
Clinical outcomes as assessed by the physicians

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.

Statistical Analysis

Descriptive statistics with Confidence


interval or percentile as appropriate

5. (a) Have the authors identified all important


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

Cant tell

No confounding factor is noted in


this study.

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.

(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 1st infusion.

Results

Results

Results

Results

Results

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 local


population?
Yes,
It would be unethical to use RCT in these
patients.
The results can be generalized.

11. Do the results of this study fit with


other available evidence?
Yes,

It is consistent with the previous study


performed in healthy volunteers.

12. What are the implications of this study for


practice?
This interim study provides the result to
support that idarucizumab can be used to
reverse the anticoagulant effects of
dabigatran.

Conclusion
Idarucizumab rapidly and completely
reversed the anticoagulant activity of
dabigatran in 88 to 98% of patients.
No safety concerns

Reference
1. Pollack CV, Reilly PA, Eikelboom J, Glund S,
Verhamme P, Bernstein R, et al. Idarucizumab
for Dabigatran Reversal. N Engl J Med
2015;373:511-20
2. Critical Apprasial Skills Programme, cohort
study checklist (2013)