Background: Angiotensin receptor blockers (ARBs), such as telmisartan, have been postulated to treat Covid-19-induced lung inflammation. Methods: This is a parallel-group, randomized, two-arm, open-label, adaptive, multicenter superiority trial with 1:1 allocation ratio. Participants included patients from 18 years of age hospitalized with Covid-19 with 4 or fewer days since symptom onset enrolled at a university and a community hospital in Buenos Aires, Argentina. Exclusion criteria included prior intensive care unit (ICU) admission and use of ARBs/angiotensin converting enzyme inhibitors at randomization. Control arm received standard care alone and treatment arm telmisartan 80 mg twice daily for 14 days. Primary outcomes were C-reactive protein (CRP) plasma levels at day 5 and 8 after randomization. Secondary outcomes included time to discharge within 15 days, admission to ICU and death at 15-and 30-days. NCT04355936 (Completed). Findings: A pragmatic decision to end the study before the third interim analysis was made on Oct. 30th due to sharp reduction in recruitment. A total of 162 patients were randomized. 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. 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. Day 5 control-group CRP levels were 6.06 § 6.95 mg/dL (95% CI 7.79À4.35, n = 66) while telmisartan group were 3.83 § 5.08 mg/dL (95% CI 5.08À2.59, n = 66, p = 0.038). Day 8 CRP levels were 6.30 § 8.19 mg/dL (95% CI 8.79À3.81, n = 44) and 2.37 § 3.47 mg/dL (95% CI 3.44À1.30, n = 43, p = 0.0098) in the control and telmisartan groups, respectively (all values expressed as mean § SD). Kaplan-Meier analysis showed that telmisartan-treated patients had a lower median time-to-discharge (control=15 days; telmisartan=9 days). Death by day 30 was reduced in the telmisartan-treated group (control 22.54%,
One of the most difficult management issues in lupus nephritis (LN) is the optimal duration of maintenance immunosuppression after patients are in clinical remission. Most patients receive immunosuppression for years, based mainly on expert opinion. Prospective data are unavailable. Complicating this issue are data that patients in clinical remission can still have histologically active LN; however, the implications of this are unknown. To study this, the Lupus Flares and Histological Renal Activity at the end of Treatment study (ClinicalTrial.gov, NCT02313974) was designed to examine whether residual histologic activity predisposes to LN flares in class III and IV LN. Patients in complete clinical remission for at least 12 months who had received at least 36 months of immunosuppression were eligible. Patients consented to a second kidney biopsy, were tapered off maintenance immunosuppression and were then followed prospectively for LN flares over 24 months. Forty-four patients were enrolled, and 36 completed the study. LN flares occurred in 11 patients, and ten of these had residual histologic activity on the second biopsy. All patients with an NIH activity index over two flared. The activity index and duration of systemic lupus erythematosus at the second biopsy were independent predictors of flare. A predictive equation based on these variables discriminated between flare and no flare with a sensitivity of 100%, specificity of 88%, and a misclassification rate of 8.3%. Thus, a repeat kidney biopsy may be useful in managing maintenance immunosuppression in LN, and patients in histologic remission may be candidates for withdrawal of therapy.
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