CS1, a controlled-release formulation of valproic acid, for the treatment of patients with pulmonary arterial hypertension: Rationale and design of a Phase 2 clinical trial.

Although rare, pulmonary arterial hypertension (PAH) is associated with substantial morbidity and a median survival of approximately 7 years, even with treatment. Current medical therapies have a primarily vasodilatory effect and do not modify the underlying pathology of the disease. CS1 is a novel oral, controlled-release formulation of valproic acid, which exhibits a multi-targeted mode of action (pulmonary pressure reduction, reversal of vascular remodeling, anti-inflammatory, anti-fibrotic, and anti-thrombotic) and therefore potential for disease modification and right ventricular modeling in patients with PAH. A Phase 1 study conducted in healthy volunteers indicated favorable safety and tolerability, with no increased risk of bleeding and significant reduction of plasminogen activator inhibitor 1. In an ongoing randomized Phase 2 clinical trial, three doses of open-label CS1 administered for 12 weeks is evaluating the use of multiple outcome measures. The primary endpoint is safety and tolerability, as measured by the occurrence of adverse events. Secondary outcome measures include the use of the CardioMEMS™ HF System, which provides a noninvasive method of monitoring pulmonary artery pressure, as well as cardiac magnetic resonance imaging and echocardiography. Other outcomes include changes in risk stratification (using the REVEAL 2.0 and REVEAL Lite 2 tools), patient reported outcomes, functional capacity, 6-min walk distance, actigraphy, and biomarkers. The pharmacokinetic profile of CS1 will also be evaluated. Overall, the novel design and unique, extensive clinical phenotyping of participants in this trial will provide ample evidence to inform the design of any future Phase 3 studies with CS1.

Efeito da inibicao da enzima conversora da angiotensina em comparacao com a terapeutica convencional sobre a morbidade e a mortalidade cardiovasculares na hipertensao: estudo randomizado Projeto Prevencao Captopril(CAPPP) / Effect of angiotensin-converting-enzime inhibition compared with conventional theraphy on cardiovascular morbidity and mortality in hypertension: the captopril Prevention Project(CAPPP) randomised trial

Os inibidores da enzima conversora da angiotensina (ECA) tem sido utilizados durante mais de uma decada para o tratamento do aumento da pressao arterial,apesar da ausencia de dados a aprtir de estudos randomizados de intervencao que tenham demosnstrado que esse tipo de tratamento afeta a morbidade e a mortalidade cardiovasculares.O trabalho denomnado Projeto Prevencao Captopril-Captopril Prevention Project(CAPPP) e um estudo randomizado de intervencao para comparacao dos efeitos da inibicao da ECA e da terapeutica convencional sobre a morbidade cardiovasculares em pacientes com hipertensao.O CAPPP foi um estudo prospectivo,randomizado de tipo aberto com avaliacao cega dos objetivos finais.Foram incluidos 10.985 pacientes em 536 centros de saude na Suecia e na Finlandia.Os pacientes com idades entre 25 e 66 anos cuja medicao da pressao arterial diastolica registrou 100 mmHg ou mais,em duas oportunidades,foram randomizados para o captopril ou para o tratamento antihipertensivo convencional(diureticos,beta-bloqueadores)