Aplicação, eficácia e segurança do Sham-CPAP em ensaios clínicos com pacientes com apneia obstrutiva do sono moderada e grave
Arquivos
Data
2017-04-28
Autores
Mello, Luciane Impelliziere Luna de 
Orientadores
Poyares, Dalva Lucia Rollemberg
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A Apneia Obstrutiva do Sono (AOS) moderada e grave, tem como principal tratamento a pressão positiva contínua nas vias aéreas (CPAP). Nos estudos clínicos randomizados (ECRs) em pacientes com a AOS, a eficácia do CPAPfoi comparada a procedimentos “placebo” não ideais. O desenvolvimento do Sham-CPAP, já foi validado, no entanto, o tempo máximo de seu uso, sua eficácia e segurança ainda não foram adequadamente avaliados. Objetivo: Verificar a eficácia e segurança do uso do Sham-CPAP durante 6 meses, em um ECR, em pacientes com AOS moderada e grave. Desenho do Estudo: ECR duplo-cego. Método: Pacientes de ambos os sexos, com diagnóstico de AOS e com índice de apneia e hipopneia (IAH) ≥ 20 eventos/hora, diagnosticados por polissonografia (PSG) de noite inteira e com idade 35-65 anos, randomizados para uso de CPAP ou Sham-CPAP. As variáveis antropométricas, polissonográficas, ecocardiográficas e laboratoriais dos pacientes tratados, foram coletadas e analisadas durante 6 meses. Os valores normais do Dióxido de Carbono (CO2) e do Dióxido de Carbono Exalado (EtCO2) foram medidos na máscara durante a noite da PSG para a titulação do Sham-CPAP. Resultados: Dos 212 pacientes com a AOS, 72 foram randomizados para o tratamento com o CPAP ou o Sham-CPAP. Não foram observadas diferenças significativas entre os grupos no momento basal, com exceção do IAH e do índice de despertares que foram maiores no grupo CPAP (31,5±11,3Sham-CPAPvs.49,3±24,7CPAP e 25,3±11,9Sham-CPAPvs35,9±19,0CPAP, p<0,001).O número de desistências foi similar nos dois grupos durante o protocolo (p=0,59). Durante o acompanhamento do grupo Sham-CPAP foi observado um aumento da Pressão Arterial Diastólica (PAD), um aumento no Índice de Massa Corpórea (IMC) e uma redução da Lipoproteína de Alta Densidade (HDL) no sexto mês do protocolo (respectivamente p<0,001; p=0,01; p=0,001). A adesão ao Sham-CPAP foi menor no sexto mês de acompanhamento, em relação aos meses anteriores. Em relação às variáveis sanguíneas, houve queda progressiva e significativa nos valores da Hemoglobina (Hg) e do Hematócrito (Ht) no grupo estudado (respectivamente p<0,001; p=0,04; p=0,01). Conclusões: Os resultados reforçam o uso do Sham-CPAP como placebo efetivo em ECRs nos pacientes com a AOS, em relação à adesão, ao cegamento e à ausência de retenção do CO2 na máscara. No entanto, o Sham-CPAP mostrou não ser seguro após o terceiro mês de tratamento, devido ao aumento da PA, do IMC e da redução do HDL.
The CPAP is the principal treatment for obstructive sleep apnea (OSA), itseffectiveness was compared to "placebo" procedures not ideals.The development of the Sham-CPAP as placebo in randomized clinical studies in OSA patients has been already validated, however, the use of Sham-CPAP, its efficacy and safety during clinical trials have not yet been properly evaluated.Objective:The objective of this study was to verify the efficacy and safety of Sham-CPAP in a 6-month randomized clinical trial in patients with moderate to severe obstructive sleep apnea (OSA).Study design: Randomized, double-blind clinical trial.Methods: Recently diagnosed OSA patients aged 35-65 years old with an apnea hypopnea index(AHI) 20 events/hwere assessed by full polysomnography (PSG) and included in a randomized 6-month clinical trial ofcontinuous positive airway pressure (CPAP) or Sham-CPAP treatment. Sham-CPAP was designed to deliver between 0.5 and 1.5 cmH2O positive pressure in the mask while maintaining the sensation of ventilation throughadaptationsto the system.We compared the anthropometric, polysomnographic, echocardiographic, and laboratory variables in patients treated with CPAP or Sham-CPAP throughout the 6 months of the study protocol. Results: We analyzed 33 patients in the Sham-CPAP group and 39 in the CPAP group. No significant differences were found between the groups at baseline, with the exception of higher AHI and arousal index in the CPAP group. 31.5±11.3Sham-CPAP vs. 49.3±24.7CPAP and 25.3 ±11.9 Sham-CPAP vs. 35.9±19.0 CPAP, p<0,001).Thedropout rate was similar in both groups throughout the protocol (p=0.59). Normal end-tidal CO2 values were found in the mask during the Sham-CPAP titration in full-night PSG. The Sham-CPAP group showed a significant increase in diastolic blood pressure (DBP) and a reduction in total cholesterol and high density lipoprotein (HDL)atthe six-monthfollow up (p<0,001; p=0.04; p=0.01 respectively). Compliance was loweratthe 6 month follow-up compared with the 1- month and 3-month periods in the Sham-CPAP group, there was no difference in the CPAP group. Blood testsshowed a significant and progressive reduction in hemoglobin (Hb) and hematocrit (Ht) in the study group (p=0.005; p<0.001 respectively).Conclusion: The results support the use of Sham-CPAP as an effective placebo control in clinical trials in OSA patients in terms of compliance, blindness, and CO2 retention in the mask. However, Sham-CPAP seemed to be safe only until the third month of treatment due to increased blood pressure, increased BMI, reduced HDL.
The CPAP is the principal treatment for obstructive sleep apnea (OSA), itseffectiveness was compared to "placebo" procedures not ideals.The development of the Sham-CPAP as placebo in randomized clinical studies in OSA patients has been already validated, however, the use of Sham-CPAP, its efficacy and safety during clinical trials have not yet been properly evaluated.Objective:The objective of this study was to verify the efficacy and safety of Sham-CPAP in a 6-month randomized clinical trial in patients with moderate to severe obstructive sleep apnea (OSA).Study design: Randomized, double-blind clinical trial.Methods: Recently diagnosed OSA patients aged 35-65 years old with an apnea hypopnea index(AHI) 20 events/hwere assessed by full polysomnography (PSG) and included in a randomized 6-month clinical trial ofcontinuous positive airway pressure (CPAP) or Sham-CPAP treatment. Sham-CPAP was designed to deliver between 0.5 and 1.5 cmH2O positive pressure in the mask while maintaining the sensation of ventilation throughadaptationsto the system.We compared the anthropometric, polysomnographic, echocardiographic, and laboratory variables in patients treated with CPAP or Sham-CPAP throughout the 6 months of the study protocol. Results: We analyzed 33 patients in the Sham-CPAP group and 39 in the CPAP group. No significant differences were found between the groups at baseline, with the exception of higher AHI and arousal index in the CPAP group. 31.5±11.3Sham-CPAP vs. 49.3±24.7CPAP and 25.3 ±11.9 Sham-CPAP vs. 35.9±19.0 CPAP, p<0,001).Thedropout rate was similar in both groups throughout the protocol (p=0.59). Normal end-tidal CO2 values were found in the mask during the Sham-CPAP titration in full-night PSG. The Sham-CPAP group showed a significant increase in diastolic blood pressure (DBP) and a reduction in total cholesterol and high density lipoprotein (HDL)atthe six-monthfollow up (p<0,001; p=0.04; p=0.01 respectively). Compliance was loweratthe 6 month follow-up compared with the 1- month and 3-month periods in the Sham-CPAP group, there was no difference in the CPAP group. Blood testsshowed a significant and progressive reduction in hemoglobin (Hb) and hematocrit (Ht) in the study group (p=0.005; p<0.001 respectively).Conclusion: The results support the use of Sham-CPAP as an effective placebo control in clinical trials in OSA patients in terms of compliance, blindness, and CO2 retention in the mask. However, Sham-CPAP seemed to be safe only until the third month of treatment due to increased blood pressure, increased BMI, reduced HDL.
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Citação
MELLO, Luciane Impelliziere Luna de. Aplicação, eficácia e segurança do Sham-CPAP em ensaios clínicos com pacientes com apneia obstrutiva do sono moderada e grave. São Paulo, 2017. [97] p. Tese (Doutorado em Psicobiologia) - Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, 2017.