Rationale and Design of PEMVITASTART—An Open-label Randomized Trial Comparing Simultaneous Versus Standard Initiation of Vitamin B12 and Folate Supplementation in Nonsquamous,Non–Small-cell Lung Cancer Patients Undergoing First-line Pemetrexed-based Chemotherapy

Pemetrexed is the preferred chemotherapeutic drug for nonsquamous, non–small-cell lung cancer patients whenever the predictive molecular biomarkers for targeted therapy have either not been assessed or are absent. As per manufacturers' instructions, supplementation with folic acid (FA; folate) at a dose of 350 to 1000 μg daily should be started seven days before the first dose of pemetrexed-based chemotherapy and continued during therapy and for 21 days after therapy cessation. Vitamin B₁₂ injections (1000 μg intramuscularly) should also be started one week before the first dose of chemotherapy. However, the evidence for delaying chemotherapy by one week for the purpose of providing vitamin B₁₂ and FA supplementation is not robust. Observational and prospective single-arm studies have not shown any increased toxicity if pemetrexed was started earlier than the recommended duration of supplementation. In a resource-constrained setting, the standard (conventional) approach would lead to one additional visit and a 1-week chemotherapy delay, both of which could be inconvenient for patients. Hence, an open-label, randomized trial (PEMVITASTART [Vitamin Supplementation in NSCLC Patients on Pemetrexed Based Chemotherapy]; ClinicalTrials.gov identifier, NCT02679443) is being undertaken to evaluate whether any differences exist in pemetrexed-related hematologic toxicity among patients who receive delayed initiation of chemotherapy (after 5-7 days of vitamin B₁₂ and FA supplementation [delayed arm]) compared with those for whom vitamin B₁₂ and FA supplementation is started simultaneously (within 24 hours) of chemotherapy initiation (immediate arm). The present report describes the rationale and detailed design of the PEMVITASART trial.     

Evaluation of intracoronary blood from obstructive vessel in patients of ST-elevation myocardial infarction undergoing PPCI

ObjectiveInformation available on acid–base imbalance in ST-elevation myocardial infarction (STEMI) submitted to primary percutaneous intervention is limited and no data were present on intracoronary blood analysis, extracted from obstructed artery.MethodsThis was a prospective study conducted over 12 months in which STEMI patients presenting in emergency and undergoing primary percutaneous coronary intervention were included. Blood gas analysis of intracoronary arterial blood from obstructed vessel and peripheral arterial blood was performed. Patients in whom adequate intracoronary sample could not be obtained were excluded. Intracoronary and peripheral arterial blood gas measurements were correlated and relationship of intracoronary parameters were compared with clinical parameters, investigational markers and short-term outcome.ResultsThe mean age of study population was 54.8 years and average symptom onset to door time was 162 min. On comparing intracoronary blood with peripheral blood arterial obtained, pH (95% confidence interval [CI] ?0.01 to 0.02;p = 0.44), lactate (95% CI 0.03–0.1;p = 0.28), bicarbonate (95% CI 0.6–1.5;p = 0.64), pCO₂ (95% CI 1.1–2.4;p = 0.79) and pO₂ (95% CI 3.2–47.5; p = 0.06) were all found to be statistically insignificant. Intracoronary hyperlactatemia was present in patients presenting with higher symptom onset to door time (p = 0.025). Systolic blood pressure (SBP) (p = 0.03) was also significantly lower in patients who had high intracoronary lactate levels.ConclusionThe evaluation of intracoronary blood provides no additional information regarding the prognosis and short-term (30-day) outcome of the patients when compared with peripheral blood. However, there was a significant intracoronary hyperlactatemia in patients presenting late after symptom onset. SBP was also significantly less in patients with high intracoronary lactate, which signifies that predominant cause of hyperlactatemia was systemic hypoperfusion rather than local increase in lactate levels.