![]() At day 5, patients in the telmisartan added to standard care group had a lower absolute CRP serum level than patients in the standard care group (standard care 6.06 ± 6.95 mg/dL, 95% CI 7.79 to 4.35, n = 66 telmisartan added to standard care 3.83 ± 5.08 mg/dL, 95% CI 5.08 to 2.59, n = 66, p = 0.038, Table 2 and Fig. ![]() Neutrophil to lymphocyte ratio median (Q1 to Q3)īaseline absolute CRP serum levels were 5.53 ± 6.19 mg/dL (95% CI 6.91 to 4.15, n = 80) and 9.04 ± 7.69 (95% CI 9.04 to 10.82, n = 74) in the standard care and telmisartan added to standard care groups, respectively (all values are expressed as mean ± SD). ESR, Erythrocyte Sedimentation Rate LMWH, low molecular weight heparin. ![]() COPD, Chronic Obstructive Pulmonary Disease CRP, C-reactive protein LDH, lactate dehydrogenase. Table 1 Demographic and clinical characteristics at baseline. After the second interim analysis, a pragmatic decision was made by RPR, MD, FP and LNN to stop the trial at 162 patients (Oct 30th, 2020) due to a sharp decrease in patient recruitment. ![]() No data specific to data were discussed on how to manage the trial, manage individual study patients, or make study assessments was shared with onsite investigators. None of these members took part in on site activities such as data gathering, enrollment and treatment. Interim analysis was carried out by FP and reviewed by RPR and MVS. To control across repeated analyses for Type I error, set at 0.05, critical values for interim testing were defined based on O'Brien-Fleming's boundaries. Early stopping due to efficacy was defined as achieving significant differences between groups in our main outcome. A third interim analysis was planned after accrual of 200 patients. A second interim analysis was conducted at recruitment of 140 patients on September 12th 2020. Added value of this studyĪ first interim analysis was conducted on July 31st 2020 with 82 patients. We adhere to this last hypothesis and we think that their evaluation in a clinical trial would be possible by choosing a pharmacologically adequate tool (telmisartan), using effective doses (160 mg / day), at an early stage of the disease (≤4 days from the onset of symptoms) in hospitalized patients not admitted to intensive care. On the other hand, the opposite was hypothesized considering that these drugs may be beneficial in COVID-19 by antagonizing either the production of angiotensin II or its pro-inflammatory effect via AT1 receptors. Previous experimental studies showed that the classical ACE inhibitor drugs and angiotensin II AT1 receptor blockers increased the expression of ACE2 and it was immediately postulated that they could be harmful, favoring the entry of SARS-CoV-2 and the severity of COVID-19. Consequently, it increases the tissue concentration of angiotensin II (pro-inflammatory stimulating AT1 receptors) and decreases that of angiotensin 1–7 (anti-inflammatory stimulating MAS receptors). SARS-CoV-2 virus enters the airway and binds through protein S (Spike) to the Angiotensin Converting Enzyme 2 (ACE2) of alveolar cells and by endocytosis, internalizes, losing its function transforming angiotensin II into angiotensin 1–7. Composite ICU, mechanical ventilation or death was reduced by telmisartan treatment at days 15 and 30. Death by day 30 was reduced in the telmisartan-treated group (control 22.54%, 16/71 telmisartan 4.29%, 3/70 participants p = 0.0023). Kaplan-Meier analysis showed that telmisartan-treated patients had a lower median time-to-discharge (control=15 days telmisartan=9 days). Baseline absolute CRP serum levels were 5.53 ± 6.19 mg/dL (95% CI 6.91 to 4.15, n = 80) and 9.04 ± 7.69 (95% CI 9.04 to 10.82, n = 74) in the standard care and telmisartan added to standard care groups, respectively. 158 patients enrolled between May 14 and October 30 2020, were included in the analysis, 80 in the standard care and 78 in the telmisartan added to standard care group. 30th due to sharp reduction in recruitment. The Lancet Regional Health – Western PacificĪ pragmatic decision to end the study before the third interim analysis was made on Oct.The Lancet Regional Health – Southeast Asia.The Lancet Gastroenterology & Hepatology.
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