CME Self-Assessment Examination

See answer key link at bottom of page

1. All of the following are postulated to be beneficial actions of cicletanine in PAH except:
   1. Natriuresis
   2. Increased nitric oxide synthesis
   3. Endothelin-A receptor cleavage
   4. Phosphodiesterase-5 inhibition
   5. Smooth muscle hyperpolarization and calcium channel inhibition
2. Tyrosine kinase inhibitors like sorafenib or imatinib are most likely to be useful as treatment for PAH by blocking:
   1. Vascular smooth muscle apoptosis
   2. Platelet degranulation
   3. Monocyte chemotaxis
   4. Endothelial cell proliferation
   5. Smooth muscle contraction (vasoconstriction)
3. In current clinical trials, endothelial progenitor cell therapy:
   1. Requires chronic immunosuppression with mycophenalate (Cell Cept)
   2. Reintroduces autologous cells after in vitro expansion of a select mononuclear cell population
   3. Offers the possibility of overexpressing specific genes in the pulmonary circulation
   4.  A and B
   5. B and C
4. The PACES study adding sildenafil to epoprostenol:
   1. Required patients to be on at least 30 ng/kg/min epoprostenol for 2 months prior to enrollment
   2. Allowed up to 4 epoprostenol dose increments during the placebo-blinded phase
   3. Measured a 41 m improvement in placebo-corrected 6MW distance for sildenafil-treated patients
   4. Measured a benefit of sildenafil on time to clinical worsening
   5. Was terminated early because sildenafil produced an unanticipated improvement in functional class for 40% of sildenafil-treated patients
5. With regard to the 6MW test as an endpoint in PAH, which of the following is most correct?
   1. The placebo-corrected improvement in 6MW distance has been a primary endpoint in most of the pivotal registration trials for approved PAH drugs
   2. There may be a "ceiling effect" with a reduced sensitivity to measure improvements in the 6MW test for patients with better baseline exercise capacity
   3. One key advantage of the 6MW is that investigators have shown that 30 m improvements in 6MW are clinically significant and substantially greater than day-to-day variation
   4. A and B
   5. B and C
6. With regard to the design of clinical research, an eventdriven clinical trial:
   1. Was used to study the addition of inhaled treprostinil to bosentan or sildenafil
   2. Requires a longer duration placebo blinded phase, especially if patients in the placebo arm have few events per unit time
   3. Is probably unethical because the 4th WHO meeting in Dana Point created consensus about the utility of 6MW distance as the best primary endpoint
   4. Will never be adopted in PAH because it requires too many patients
7. Which of the following statements about epoprostenol is most correct?
   1. The pivotal registration trial was double blind
   2. Epoprostenol is FDA-approved for patients in functional class II-IV
   3. The drug requires daily mixing and the infusion must be chilled with ice packs or changed frequently
   4. B and C
   5. None of the above
8. In the placebo-controlled trials for oral beraprost:
   1. The placebo-corrected improvement in 6MW distance was improved in the North American and European trials at 3 months
   2. The improvement in placebo-corrected 6MW test was the primary endpoint for both the European and North American studies
   3. Each trial enrolled more than 200 patients
   4. The European trial dosed patients 6 times daily because of the short beraprost half-life
   5. The drug was well tolerated with modest side effects that did not limit the dose achieved
9. With regard to the pharmacokinetic data for beraprost and UT-15C (oral treprostinil diethanolamine), which of the following is most correct?
   1. Peak beraprost levels occur 2 hours after a dose, provided that a 500-calorie meal is ingested with the drug
   2. UT-15C produced near maximum treprostinil levels in most patients 30 minutes after the drug was dosed
   3. Many patients taking UT-15C have achieved sustained serum treprostinil levels similar to patients on 60 ng/kg/min of parenteral treprostinil
   4. At higher doses (3-4 mg BID), UT-15C patients have clinically relevant serum treprostinil levels for ~6 hours during the 12 hours following a dose
   5. The smaller UT-15C tablet strengths (0.25 mg, 0.5 mg) have a shorter half-life than the original 1 mg tablet strength