Journal Club

Sidharth Bagga MD

Cytisus laborium L. (Golden rain acacia)

Case CC: “I’d like to quit, but it is cheaper to keep smoking” 56 male with 20 pack year smoking history

Seen in clinic in follow up Has had 4 unsuccessful attempts at quitting smoking Hx of HTN Patient is a construction worker and not very eager to spend his beer

money on smoking cessation treatment anymore So what do you do now?

1. Smoking cessation tricks (impotence, wrinkles, etc) 2. Ask, document and move on 3. Varencycline 4. Nicotine replacement 5. New non approved Cytisine

Background / Context? Smoking Prevalence

1960s – 42% to 2010s – 20%

Tobacco use remains chief avoidable cause of death in US Many clinicians do not offer smoking cessation Only 20% of smokers are ready to attempt quit at any time 95% of unaided attempts fail Pts typically consume 50% of recommended dose of medications Only complete about half of smoking cessation counseling

Treatment availability / ease of use? If treatment delayed or separate location, only 10% follow through If same location and immediate, 1/3rd follow through

Schweikert et al, Lancet, 2009

Cytisine Nicotine

Journal Club

Research Question

Assess Cytisine’s efficacy and safety in a context that could be

replicated globally relatively short treatment goal (25 days) minimal contact with health professionals.

Design / Subjects Prospective, randomized, single center, double-

blind trial between 12/2007 & 9/2010 in Poland.

Inclusion Criteria Adults smoke > 10 cigs/day + willing to stop permanently,

literate, provide consent Exclusion Criteria

Pregnancy, breast feeding, current psychiatric d/o, medical contraindication for Cytisine (arterial HTN + advanced arteriosclerosis)

Sampling No other smoking cessation drugs current Relapse: > 5 cigs used since enrollment, no smoking in last

week, breath CO < 10ppm

Study Procedures Variable block randomization (eliminates early/late bias) First Visit

Age, sex, employment, marital status, Nicotine Dependence (FTND), # of cigs/day, duration of smoking, & quit attempts

Beck Depression Inventory

6 months Phone contacts If abstinent: return to clinic, CO in exhaled breath, Depression

12 months (same) Adverse Reactions

Asked, if ‘Yes’ then verbatim copied and compiled according to standard adverse reaction data

Measurements - Outcomes Primary Outcome

12 month of abstinence from smoking Changed from original 6 months before unblinding/data

analysis

Secondary Outcome Abstinence at 6 months and point prevalence at 12

months (week before visit)

Criteria for abstinence Fewer than 5 cig in last 6 months Confirmed with less than 10 ppm of CO in exhaled

breath

Statistical Analysis Sample Size

Calculated need for 740 pts to show a difference of 6 points b/w groups to show percentage reduction in abstinence with 80% power & p < .05

Intention to treat analysis Categorical variables – x2 and Fischer Exact test Logistic regression to examine efficacy with adjustment

from baseline characteristics P < .05 was considered statistically significant

Study Enrollment & Follow Up

Baseline Characteristics

Cytisine administration

6 tabs/day

5 tabs/day

4 tabs/day 3 tabs/day 2 tabs/day

DAY 1-3 DAY 4-12 DAY 13-16 DAY 17-20 DAY 20-25

QUIT DATETotal: 101 tablets

Study Procedures

Results

Adverse Events

Discussion Evidence of efficacy of Cytisine as an aid in

smoking cessation More gastrointestinal adverse events Rate of discontinuation / dose reduction (same as placebo)

Relative Rate Cytisine (3.4) higher than Varenicline (2.3) & Nicotine (1.6)

Absolute rate of Abstinence Lower than varenicline, but similar to nicotine replacement

Treatment period (4, 6, 8, 12 weeks)

May reduce cravings & make cigs less satisfying, like Varenicline (a2b4 receptor)

Limitations Adults with previous attempts? Which medications?

Outcomes at 12 weeks? Standard for other drug regimens

Need to compare to current standard of care

Conclusion Cytisine needs FDA approval

Studies to assess efficacy in conjunction with cognitive feedback

Cheap, effective alternative

JAMA Article Assesment: Therapy Are the results of the study valid?

Was the assignment of patients to treatments randomized? Yes Were all pts who entered the trial properly accounted for and attributed at its

conclusion? Yes Was follow-up complete? Yes Were pts analyzed in the groups to which they were randomized? Yes Were patients, health workers, and study personnel blind to treatment? Yes Were the groups similar at the start of the trial? Yes Aside from the experimental intervention, were the groups treated equally? Yes

What were the results? How large was the treatment effect? How precise was the estimate of the treatment effect?

Will the results help me in caring for my patients? Can the results be applied to my patient care? Yes (bulgarian drugs) Were all clinically important outcomes considered? SOME Are the likely treatment benefits worth the potential harms and costs?

Yes

JAMA Article Assesment: Therapy