Introduction In vitro studies have shown the efficacy of Ivermectin (IV) to inhibit the SARS - CoV- 2 viral replication, but questions remained as to In-vivo applications. We set out to explore the efficacy and safety of Ivermectin in persons infected with COVID19. Methods We conducted a translational proof of concept (PoC) randomized, double blind placebo controlled, dose response, parallel group study of IV efficacy in RT - PCR proven COVID 19 positive patients. 62 patients were randomized to 3 treatment groups. (A) IV 6mg regime, (B)IV 12 mg regime (given Q84hrs for 2weeks) (C, control) Lopinavir/Ritonavir. All groups plus standard of Care. Results The Days to COVID negativity [DTN] was significantly and dose dependently reduced by IV (p = 0.0066). The DTN for Control were, = 9.1+/-5.2, for A 6.0 +/- 2.9, and for B 4.6 +/-3.2 . 2 Way repeated measures ANOVA of ranked COVID 19 +/- scores at 0, 84, 168, 232 hours showed a significant IV treatment effect (p = 0.035) and time effect (p < 0.0001). IV also tended to increase SPO2% compared to controls, p = 0.073, 95% CI - 0.39 to 2.59 and increased platelet count compared to C (p = 0.037) 95%CI 5.55 - 162.55 × 103/ml. The platelet count increase was inversely correlated to DTN (r = -0.52, p = 0.005). No SAE was reported. Conclusions 12 mg IV regime may have superior efficacy. IV should be considered for use in clinical management of SARS-Cov-2, and may find applications in community prophylaxis in high-risk areas.
IntroductionIn vitro studies have shown the efficacy of Ivermectin (IV) to inhibit the SARS - CoV-2 viral replication, but questions remained as to In-vivo applications. We set out to explore the efficacy and safety of Ivermectin in persons infected with COVID19.MethodsWe conducted a translational proof of concept (PoC) randomized, double blind placebo controlled, dose response, parallel group study of IV efficacy in RT - PCR proven COVID 19 positive patients. 62 patients were randomized to 3 treatment groups. (A) IV 6mg regime, (B)IV 12 mg regime (given Q84hrs for 2weeks) (C, control) Lopinavir/Ritonavir. All groups plus standard of Care.ResultsThe Days to COVID negativity [DTN] was significantly and dose dependently reduced by IV (p = 0.0066). The DTN for Control were, = 9.1+/−5.2, for A 6.0 +/− 2.9, and for B 4.6 +/−3.2. 2 Way repeated measures ANOVA of ranked COVID 19 + / − scores at 0, 84, 168, 232 hours showed a significant IV treatment effect (p=0.035) and time effect (p <0.0001). IV also tended to increase SPO2 % compared to controls, p = 0.073, 95% CI - 0.39 to 2.59 and increased platelet count compared to C (p = 0.037) 95%CI 5.55 - 162.55 × 103/ml. The platelet count increase was inversely correlated to DTN (r = −0.52, p = 0.005). No SAE was reported.Conclusions12 mg IV regime may have superior efficacy. IV should be considered for use in clinical management of SARS-Cov-2, and may find applications in community prophylaxis in high-risk areas.
The efficacy of ivermectin (IVM) against SARS-CoV-2 has been demonstrated in vitro, while several clinical studies suggest that it is efficacious and safe in reducing morbidity and mortality. Hydroxychloroquine HCQ, IVM and azithromycin AZM (HIA therapy) are being used in several low- and middle-income countries (LMICs) where more expensive medications such as remdesivir are out of reach. In this study, we set out to compare the efficacy of IVM monotherapy with HIA combination therapy. Methods: This was a single-blind, randomized control trial of 2 parallel groups of COVID-19-positive Nigerians. Thirty patients received ivermectin 200 mcg/kg daily for five days, while 31 patients received HIA triple therapy. The viral cycle threshold (Ct) at pretreatment baseline and days 2, 5 14 and 21 were measured for the E- and N-genes. SPO2 was assessed on a daily basis, while inflammatory markers erythrocyte sedimentation rate (ESR), C-reactive protein, and D-dimer and neutrophil/lymphocyte ratios (NLRs) were assessed at baseline and day 7. Clinical status was self-assessed daily on a Likert scale. Results: Two-way repeated measures analysis of variance (RAMOVA) did not show any difference between the two groups. However, there was a significant time effect (improvement over time) for SPO2, Ct N-gene, Ct E-gene and clinical status in both groups and significant reductions in inflammatory markers by day 7. (P<0.0001). Conclusions: AZT + HCQ may be a redundant adjuvant in COVID-19 therapy. Improvements noted are likely due in large part to ivermectin virucidal and anti-inflammatory actions.
Background and Objectives: Hypoxemic respiratory failure is a common mode of demise in Covid 19 disease. We aimed to describe the time course of SPO2 changes in Covid 19 patients treated with and without ivermectin.Methods: This was a parallel group, prospective comparative study of propensity matched Covid 19 patients (Cycle threshold Ct < 25, SPO2 < 94%). 21 of the patients received Ivermectin (IVM) inclusive regime at 12 mg daily for 5 days, while 26 others received Non-ivermectin inclusive regime ( NIVM).Results: the IVM group demonstrated earlier and greater increase in SPO2 (p=0.000) which paralleled greater and faster virological clearance (p = 0.000) on Repeat measures Analysis of Variance RMANOVA. There was a significant correlation between absolute SPO2 and absolute Ct on day 5 (r = 0.77 ) and day 7 (r = 0.77) both p = 0.000. Incremental SPO2 also correlated with incremental Ct. by day 5 ( r = 0.397, p = 0.003) and day 7 ( r = 0.315 , p = 0.0002) relative to baseline. Increase in platelet count correlated with increased SPO2 (r = 0.252, p = 0.029) on IVM, but negatively with NIVM (r = - 0.28, p = 0 .17). Inflammatory markers such as ESR, CRP or D- dimer showed no significant correlation with SPO2. Increase in SPO2 on IVM was magnified in males.Conclusion: IVM regime appears to be associated with faster and greater increase in SPO2 paralleling faster viral clearance in Covid 19 patients.
Aim: To compare outcomes from ivermectin (IVM)- and non-ivermectin (NIVM)-based treatments for COVID-19 in Abuja, Nigeria.Methods: Sixty-one consecutive virology-proven cases were recruited and managed with IVM-based regimes. A subsequent cohort of 26 patients was treated with NIVM due to physician preference, with varying combinations of lopinavir/ritonavir (Alluvia), remdesivir, azithromycin, and enoxapramin. All patients received zinc sulfate, vitamin C and supportive therapy. Propensity matching was carried out as indicated, and Repeat Measures Analysis of Variance (RMANOVA) allowing for time*treatment interaction was carried out for time dependent variables, deriving Likelihood Ratio (LR) and P values.Main outcome measures: Change in cycle threshold (viral load) over time, positivity status by day 5, improvement in clinical status using myalgia scores, days to discharge (DTD), change in SpO2 and death. Results: IVM was associated with a greater and faster reduction in viral clearance (LR=64.2 p= 0.000 for the N gene): 31% and 95% were negative by days 5 and 14, respectively, versus 0% on NIVM. The mean DTD on IVM was 8.8 days versus 19.4 days, p= 0.000. IVM proved significantly superior for Myalgia scores, LR= 23.45, P=0.0007. The mortality rate was 0/61 (0%) in IVM but 4/26 (15.3%) in NIVM. Three of the 4 deaths were in females, and 2 had been vaccinated, one fully. The SP02% increased significantly more on IVM (p < 0.0001 RMANOVA) than the NIVM group. C-reactive protein and D-dimer levels dropped significantly more sharply during IVM (P= 0.0068, 0.063), suggesting anti-inflammatory and antifibrinolytic activity.Conclusions: The IVM-based regimen caused earlier discharge from treatment and reduced mortality, in addition to clinical and laboratory improvements. Vaccination did not protect some patients from SARS-CoV-2 breakthrough infection and mortality.
Background and aims. The covid 19 pandemic necessitated the use of old, repurposed, and new drugs, in addition to vaccines and public health measures. There are still many controversies about the efficacy and impact of some of the medications used, which need further elucidation. We review the pharmacological properties and the place of the repurposed drug, Ivermectin (IVM) in the prophylaxis and treatment of SARS - CoV- 2 (severe acute respiratory syndrome coronavirus 2.) infection or Covid 19 disease. Major findings: in-vitro, in-vivo, and human studies In vitro studies in Vero/hSlam cells caused a 99.98 % inhibition of SARS - Cov-2 (5000-fold) within 48 hours. The IC50 (half maximal inhibitory concentration) for this virucidal action was 2.8μM, which was thought unattainable in humans in-vivo. Thus, there was initial skepticism on pharmacokinetic grounds as to possible efficacy of IVM in humans with Covid 19. There are, however, a multiplicity of anti-covid 19 mechanisms, beyond mere anti-viral effects, such as blockade of ACE2 receptor viral entry, and the anti-cytokine and anti-inflammatory effects of IVM. IVM has a long half-life of 18 - 24 hours, Mean Residence Time (MRT) of 3.4 days and a preferential site of lung accumulation. In-vivo studies in Syrian Golden hamsters confirmed the symptomatic, anti-inflammatory, anti-cytokine, histopathological and survival benefit of IVM, which was more manifest in female animals. In a January 2023 meta-analysis of studies (s) in total number of patients (n) for various parameters (p), the reduction in risk relative to placebo or controls were as follows: Overall improvement (s= 95) (n= 134,554) was 62% [95%CI 54-69]. Mortality (s=48) (n=120,000) there was 51% reduction [95%CI 37-62]. Hospitalization (s=29) (n = 44, 784), there was 34% reduction [ 95% CI 20-45]. Viral clearance (s=20) (n= 3945) there was 45% reduction [95%CI 31-55]. Prophylaxis (s=17) (n=19,764) showed 82% reduction [95%CI 73-88] 6 Randomised Control Trial (RCT) studies (s= 45) (n=2173) showed a 54 % mortality reduction [95% CI 39-65] In addition, IVM has been shown in studies to cause a rapid reversal of hypoxemia (SPO2 < 94%) and a rapid increase in SPO2, an effect exhibiting a gender dichotomy. (SPO2 is the percentage of the maximum carrying capacity of the blood). This effect on SPO2 has been attributed to IVM’s reversal and prevention of SARS-CoV-2 virus induced hemagglutination. The dosage used for treatment of covid 19 varied widely within studies, but doses of 200-400 μg/kg twice weekly or daily for 5 consecutive days, caused significant viral clearance and clinical improvement, with minimal safety concerns. For prophylaxis, a dose of 200μg/kg for two consecutive days every 15 days was found effective in studies. Conclusion: This review provides powerful evidence that IVM is efficacious singly or as a part of a regimen for covid 19. IVM could potentially be combined with newer oral anti-covid 19 agents, such as Paxlovid, for effective and life-saving regimen in patients infected with covid-19. The anti-viral properties of these drugs can synergize with the anti-inflammatory and anti-cytokine properties of Ivermectin. Ivermectin is also useful prophylactically, especially where vaccines are unavailable or undesirable.
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