The Efficacy of the Mineralcorticoid Receptor Antagonist Canrenone in COVID-19 Patients
Abstract
:1. Introduction
2. Experimental Section
2.1. Population Description, Treatments, and Biochemical Evaluation
2.2. Statistical Method
3. Results
3.1. Patients and Clinical Course
3.2. Impact of Canrenone Administration
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Characteristics | Overall Population (n = 69) | Group A (n = 39/69) | Group B (n = 30/69) | Group A vs. Group B | Cohen’s d |
---|---|---|---|---|---|
General characteristics | |||||
Sex, m (%) | 50 (72) | 26 (67) | 24 (80) | 0.219 c | |
Age, years, mean ± SD | 61 ± 12 | 60 ± 12 | 62 ± 12 | 0.311 w | 0.13 |
Hypertension, n (%) | 31 (45) | 18 (46) | 13 (43) | 0.815 c | |
Dyslipidemia, n (%) | 14 (20) | 8 (21) | 6 (20) | 0.958 c | |
Obesity, n (%) | 16 (23) | 9 (23) | 7 (23) | 0.980 c | |
Cardiovascular disease, n (%) | 8 (12) | 5 (13) | 3 (10) | 1.000 § | |
Clinical assessment at baseline | |||||
PaO2/FiO2, mmHg, median (IQR) | 190 (99) | 182 (110) | 214 (116) | 0.023 * | 0.47 |
ΔA-aO2, mmHg, median (IQR) | 219 (102) | 234 (151) | 197 (86) | 0.133 * | 0.40 |
meanBP, mmHg, mean ± SD | 97 ± 13 | 97 ± 13 | 96 ± 13 | 0.406 w | 0.03 |
[K+]plasma, mmol/L, mean ± SD | 4.1 ± 0.5 | 4.2 ± 0.6 | 4.0 ± 0.4 | 0.111 w | 0.38 |
CRP, mg/dL, median (IQR) | 12 (10) | 11 (10) | 13 (10) | 0.186 * | 0.28 |
IL-6, pg/mL, median (IQR) | 83 (91) | 88 (139) | 83 (64) | 0.757 * | 0.16 |
D-dimer, µg/L, median (IQR) | 992 (1079) | 939 (890) | 1057 (1135) | 0.215 * | 0.33 |
Ferritin, ng/mL, median (IQR) | 1421 (2121) | 1262 (2495) | 1704 (1866) | 0.380 * | 0.02 |
In-hospital treatment distribution | |||||
ACEIs or ARBs, n (%) | 25 (36) | 6 (15) | 19 (63) | <0.001 c | |
Ca2+ channel blockers, n (%) | 11 (16) | 11 (28) | 0 (0.0) | 0.002 § | |
alpha-1-adrenergic antagonist, n (%) | 4 (6) | 4 (10) | 0 (0.0) | 0.127 § | |
Hydroxychloroquine, n (%) | 69 (100) | 39 (100) | 30 (100) | - | |
Lopinavir/Ritonavir, n (%) | 24 (35) | 23 (59) | 1 (3) | <0.001 * | |
Anakinra, n (%) | 20 (29) | 9 (23) | 11 (37) | 0.217 * | |
Cortisone, n (%) | 24 (35) | 10 (26) | 14 (47) | 0.069 * |
Dependent Variable | Treatment | Mean Baseline | Mean T1 | p–Value of Comparison Baseline vs. T1 | Overall p-Value | |
---|---|---|---|---|---|---|
Group | (95% CI) | (95% CI) | ||||
ΔA-aO2 | A | 223 (194–255) | 135 (92–198) | 0.014 | Time | <0.001 |
B | 195 (167–228) | 107 (71–162) | 0.006 | Treatment | 0.241 | |
Time * treatment | 0.735 | |||||
PaO2/FiO2 | A | 171 (152–192) | 194 (155–242) | 0.261 | Time | 0.022 |
B | 209 (183–239) | 272 (213–345) | 0.034 | Treatment | 0.011 | |
Time * treatment | 0.420 | |||||
meanBP | A | 96 (92–100) | 93 (89–98) | 0.429 | Time | 0.021 |
B | 95 (91–100) | 88 (83–94) | 0.018 | Treatment | 0.279 | |
Time * treatment | 0.187 | |||||
[K+]plasma | A | 4.2 (4–4.4) | 4.6 (4.4–4.8) | 0.005 | Time | <0.001 |
B | 4.0 (3.8–4.2) | 4.7 (4.5–4.9) | <0.001 | Treatment | 0.684 | |
Time * treatment | 0.188 | |||||
CRP | A | 8.7 (6.7–11.2) | 2.2 (1.1–4.4) | <0.001 | Time | <0.001 |
B | 12.3 (9.2–16.5) | 0.6 (0.3–1.2) | <0.001 | Treatment | 0.083 | |
Time * treatment | 0.002 | |||||
IL–6 | A | 81 (57–116) | 13 (4–43) | 0.005 | Time | <0.001 |
B | 71 (48–103) | 6 (3–12) | <0.001 | Treatment | 0.1852 | |
Time * treatment | 0.3792 | |||||
D–dimer | A | 884 (607–1287) | 2224 (1325–3731) | 0.003 | Time | 0.112 |
B | 1426 (929–2189) | 1164 (651–2083) | 0.547 | Treatment | 0.745 | |
Time * treatment | 0.014 | |||||
Ferritin | A | 1259 (881–1800) | 1109 (664–1852) | 0.668 | Time | 0.375 |
B | 1328 (884–1996) | 1021 (588–1772) | 0.416 | Treatment | 0.952 | |
Time * treatment | 0.755 |
Variable | HR for Death (95% CI) | p–Value | Variable | HR for Composite Outcome (95% CI) | p–Value |
---|---|---|---|---|---|
Model 1 | |||||
Treatment Group (B vs. A) | 0.08 (0.01–0.48) | 0.006 | Treatment Group (B vs. A) | 0.25 (0.07–0.87) | 0.030 |
Age, years | 1.09 (1.02–1.17) | 0.012 | Sex (male vs. female) | 1.09 (0.44–2.71) | 0.854 |
Sex (male vs. female) | 5.17 (1.07–24.9) | 0.041 | Dyslipidemia (yes vs. no) | 2.09 (0.88–4.98) | 0.095 |
Hypertension (yes vs. no) | 2.78 (0.73–10.6) | 0.133 | PaO2/FiO2, mmHg | 1 (0.99–1) | 0.180 |
Dyslipidemia (yes vs. no) | 1.18 (0.32–4.4) | 0.803 | ACEIs or ARBs (yes vs. no) | 0.58 (0.18–1.92) | 0.373 |
Obesity (yes vs. no) | 4.83 (1.35–17.3) | 0.016 | Lopinavir/Ritonavir (yes vs. no) | 1.21 (0.45–3.24) | 0.712 |
PaO2/FiO2, mmHg | 1 (0.99–1.01) | 0.299 | |||
Lopinavir/Ritonavir (yes vs. no) | 0.83 (0.18–3.86) | 0.815 | |||
Model 2 | |||||
Treatment Group (B vs. A) | 0.07 (0.04–0.53) | <0.001 | Treatment Group (B vs. A) | 0.19 (0.07–0.53) | 0.002 |
Age, years | 1.1 (1.04–1.16) | 0.002 | Dyslipidemia (yes vs. no) | 2.52 (1.08–5.89) | 0.032 |
Sex, (male vs. female) | 7.8 (1.88–32.6) | 0.005 | |||
Hypertension (yes vs. no) | 3.72 (1.19–11.61) | 0.024 | |||
Obesity (yes vs. no) | 3.39 (1.22–9.41) | 0.019 |
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Vicenzi, M.; Ruscica, M.; Iodice, S.; Rota, I.; Ratti, A.; Di Cosola, R.; Corsini, A.; Bollati, V.; Aliberti, S.; Blasi, F. The Efficacy of the Mineralcorticoid Receptor Antagonist Canrenone in COVID-19 Patients. J. Clin. Med. 2020, 9, 2943. https://doi.org/10.3390/jcm9092943
Vicenzi M, Ruscica M, Iodice S, Rota I, Ratti A, Di Cosola R, Corsini A, Bollati V, Aliberti S, Blasi F. The Efficacy of the Mineralcorticoid Receptor Antagonist Canrenone in COVID-19 Patients. Journal of Clinical Medicine. 2020; 9(9):2943. https://doi.org/10.3390/jcm9092943
Chicago/Turabian StyleVicenzi, Marco, Massimiliano Ruscica, Simona Iodice, Irene Rota, Angelo Ratti, Roberta Di Cosola, Alberto Corsini, Valentina Bollati, Stefano Aliberti, and Francesco Blasi. 2020. "The Efficacy of the Mineralcorticoid Receptor Antagonist Canrenone in COVID-19 Patients" Journal of Clinical Medicine 9, no. 9: 2943. https://doi.org/10.3390/jcm9092943