1. Alcohol, Other Drugs, and Health: Current Evidence
Journal Club
Alcohol, Other Drugs, and Health: Current Evidence
September-October, 2017

2. Buprenorphine for the treatment of the neonatal abstinence syndrome.
Featured Article
Buprenorphine for the treatment of the neonatal abstinence syndrome.
Kraft WK, et al. N Engl J Med. 2017;376(24):2341–2348.

3. Study Objectives
To “compare sublingual buprenorphine with oral morphine with respect to the duration of treatment in infants with the neonatal abstinence syndrome.”

4. Study Design
Randomized, double-blind, double-dummy trial at a single site in the US.
Of 121 eligible infants, 63 were enrolled.
Buprenorphine group: 33
Morphine group: 30

5. Assessing Validity of an Article about Therapy
Are the results valid?
What are the results?
How can I apply the results to patient care?

6. Are the Results Valid? Were participants randomized?
Was randomization concealed?
Were participants analyzed in the groups to which they were randomized?
Were participants in the intervention and control groups similar?

7. Are the Results Valid? (cont‘d)
Were participants aware of group allocation?
Were outcome assessors aware of group allocation?
Was follow-up complete?

8. Were participants randomized?
Yes.
Infants “were randomly assigned in a 1:1 ratio to receive either sublingual buprenorphine or oral morphine and the corresponding placebo. Randomization was stratified according to maternal exposure to methadone or buprenorphine and the maternal intention to breast-feed or bottle-feed.”

9. Was randomization concealed?
Yes.

10. Were participants analyzed in the groups to which they were randomized?
Yes.

11. Were the participants in the intervention and control groups similar?
Yes.

12. Were participants aware of group allocation?
No, the study used a double dummy design.

13. Were outcome assessors aware of group allocation?
Not stated.

14. Was follow-up complete?
No.
5 infants withdrew from the study after randomization but were included in the intention-to-treat analysis. They were excluded from the per-protocol analysis.
Overall, 13 adverse events occurred. There were no differences between the 2 groups with regard to adverse events.

15. How large was the treatment effect?
What Are the Results?
How large was the treatment effect?
How precise was the estimate of the treatment effect?

16. How large and precise was the treatment effect?
Using an intent-to-treat analysis, the median duration of treatment was significantly shorter with buprenorphine than with morphine (15 days versus 28 days, 95% confidence interval [CI], 7 to 21; P<0.001).
Median length of hospital stay was shorter in the buprenorphine group (21 days versus 33 days, 95% CI, 7 to 22; P<0.001). 16

17. How Can I Apply the Results to Patient Care?
Were all clinically important outcomes considered?
Are the likely treatment benefits worth the potential harm and costs?

18. Were all clinically important outcomes considered?
Preterm infants and those with in utero exposure to benzodiazepines were excluded.
Longer term outcomes were not assessed.

19. Are the likely treatment benefits worth the potential harm and costs?
Although there were adverse events in both groups, there was no difference found between groups in respect to harm.
Shortened hospital stays for neonatal abstinence syndrome treatment could translate to a reduction in overall treatment cost.