RESUMEN
Randomized double-blind placebo-controlled trials (RCTs) are regarded as the gold standard for clinical trials. While there are established standards to avoid unblinding, in RCTs using tetrahydrocannabinol (THC) containing cannabinoids, however, accidental unblinding and intentional self-unbinding must be considered as a particular issue, since THC tests are widely available. To investigate unblinding rates in an RCT using a THC-containing cannabinoid, we re-contacted 54 out of 97 participants of the CANNA-TICS trial who had participated in our study center in Hannover. Of the 54 participants, 53 could be reached. Of these, one participant (2%) stated that she had unblinded herself intentionally during the treatment phase, and another three patients (6%) reported intentional unblinding after the end of the treatment. Noteworthy, two patients provided discrepant information and denied self-unblinding during the interview, although during study/clinic visits they had reported having done so. Thus, based on all available information, three participants (6%) unblinded themselves intentionally during the treatment phase and another three (6%) after the end of the treatment. Accidental unblinding during the treatment phase was reported by 4/54 participants (7%) (during study visits). Since one participant reported both intentional self-unblinding (during the interview) and accidental unblinding (during a study visit), the total unblinding rate was 17% (n = 9). Of these, seven participants (13%) reported unblinding during the treatment phase. When asked in the interview whether they knew that self-unblinding would have been possible, only 34% (n = 18/53) of participants stated that they had been aware of this possibility. Thus, altogether 33% (n = 6/18) of those being informed about the possibility of self-unblinding did so and half of them (3/18, 17 %) during the treatment phase. It can be expected that in parallel to increasing knowledge of medicinal and recreational use of cannabinoids, more and more people will also be informed about the availability of THC tests. Hence, in future RCTs using THC-containing cannabinoids, researchers have to take the possibility of accidental and intentional unblinding into consideration, when designing the study.
RESUMEN
BACKGROUND: Late Fontan survivors are at high risk to experience heart failure and death. Therefore, the current study sought to investigate the role of non-invasive diagnostics as prognostic markers for failure of the systemic ventricle following Fontan procedure. METHODS: This monocentric, longitudinal observational study included 60 patients with a median age of 24.5 (19-29) years, who were subjected to cardiac magnetic resonance imaging, echocardiography, cardiopulmonary exercise testing, and blood analysis. The primary endpoint of this study was decompensated heart failure with symptoms at rest, peripheral and/or pulmonary edema, and/or death. RESULTS: During a follow-up of 24 months, 5 patients died and 5 patients suffered from decompensated heart failure. Clinical (NYHA class, initial surgery), functional (VO2 peak, ejection fraction, cardiac index), circulating biomarkers (N-terminal pro brain natriuretic peptide), and imaging parameters (end diastolic volume index, end systolic volume index, mass-index, contractility, afterload) were significantly related to the primary endpoint. Multi-variate regression analysis identified afterload as assessed by cardiac magnetic resonance imaging as an independent predictor of the primary endpoint (hazard ratio 1.98, 95% confidence interval 1.19-3.29, p = 0.009). CONCLUSION: We identified distinct parameters of cardiopulmonary exercise testing, cardiac magnetic resonance imaging, and blood testing as markers for future decompensated heart failure and death in patients with Fontan circulation. Importantly, our data also identify increased afterload as an independent predictor for increased morbidity and mortality. This parameter is easy to assess by non-invasive cardiac magnetic resonance imaging. Its modulation may represent a potential therapeutic approach target in these high-risk patients.
