A Randomized Trial - Intensive Treatment Based in Ivermectin and Iota-Carrageenan as Pre-Exposure Prophylaxis for Covid- 19 in Healthcare Agents

Abstract

IMPORTANCE: The emergency of COVID-19 requires the implementation of urgent strategies to prevent the spread of the disease, mainly in health personnel, who are the most exposed and has the highest risk of becoming infected with the SARS-COV-2. Drug repurposing is a pragmatic strategy, a faster and cheaper option, compared to the new drug development that has proven successful for many drugs and can be a key tool in emergency situations such as the current one that requires quick action. In addition, considering the limited access to vaccines for developing countries, preventive use of ivermectin can be a palliative that minimizes the risks of infection. OBJECTIVE: To evaluate the protective effect of the combination Ivermectin / Iota- Carrageenan (IVER/IOTACRC), intensive treatment with repeated administration in oral- and nasal-spray, respectively, as a prophylaxis treatment prior to exposure to SARS-CoV-2, in health personnel at Public Healthcare Centers. PARTICIPANTS, DESIGN AND SETTING: Randomized controlled 1-1 clinical trial in Personal Health, n = 234. The subjects were divided into experimental (EG: n=117; 39.6 ± 9.4 years old, 65F) and control groups (CG: n=117; 38.4 ± 7.4 years old, 61F). The EG received Ivermectin orally 2 tablets of 6 mg = 12 mg every 7 days, and Iota-Carrageenan 6 sprays per day for 4 weeks. All participants were evaluated by physical examination COVID-19 diagnosed with negative RT-PCR at the beginning, final, and follow-up of the protocol. Differences between the variables were determined using the Chi-square test. The proportion test almost contagious subject and the contagion risk (Odds Ratio) were calculated using software STATA. The level of statistical significance was reached when p-Value < 0.05. RESULT: The number of subjects who were diagnosed with COVID-19 in EG was lower, only 4 of 117 (3.4%) than subjects in CG: 25 of 117 (21.4%) (P-Value = 1.10-5). Nineteen patients had mild symptoms, 4 were in EG whereas, 15 were in CG (p-Value = 0.001). Seven subjects were moderate, and 3 with severe diagnostics, all them in CG. The probability (Odds Ratio) of becoming ill with COVID-19 was significantly lower in EG with values of 0.13, 95% 0.03 to 0.40; p-Value = 1.10-4, this value (<1) indicates a protective effect of the IVER/IOTACRC in the EG. Logistic regression test demonstrated that treatment was effective to prevent COVID-19 (Odds Ratio 0.11, 95% 0.03 to 0.33; p-Value = 1.10-4). We also found that when increase the age, decrease contagious risk (Odds Ratio 0, 93, 95% 0.88 to 0.98, p-Value= 0, 02). On the other hand, the probability of contracting COVID-19 was dependent on the patient's preexisting comorbidity (Odds Ratio 5.58, 95% 2.20 to 14.16, p-Value = 1.10-5). The other variables sex and designation were independent. CONCLUSION: The intensive preventive treatment (short-term) with IVER/IOTACRC was able to reduce the number of health workers infected with COVID-19. This treatment had also effect in preventing the severity of the disease, since all patients treated were mild. We propose a new therapeutic alternative for prevention and short-term intervention scheme (intensive) that is of benefit of the health worker in this pandemic accelerated time. This intervention did not produce lack of adherence to treatment or adverse effects.

Ivermectin: a multifaceted drug of Nobel prize-honoured distinction with indicated efficacy against a new global scourge, COVID-19

“…Supporting the findings of IVM efficacy in COVID-19 treatment as summarized above were indications of activity against SARS-CoV-2 in prevention studies. Three RCTs evaluated the prophylactic effect of IVM administered to cohorts of 100 [ 22 ], 117 [ 39 ] and 203 [ 40 ] subjects exposed to COVID-19 patients. These studies, all using IVM in doses of at least 150 μg/kg per week, reported statistically significant reductions in COVID-19 incidences, with respective RRs of 20%, 26% and 13% as compared with controls, and greater reductions in incidences of moderate and severe cases.…”

The antiviral activity of iota-, kappa-, and lambda-carrageenan against COVID-19: A critical review

“… 94 The treated group also had a lower prevalence of mild to moderate COVID-19 presentation compared to the control group. 94 This intensive preventive treatment with iota-carrageenan and ivermectin was able to significantly reduce the number of infected health care workers. 94 The study using iota-carrageenan in a single dose is still ongoing under the register numbers NCT04793984, NCT04681001, and NCT04590365.…”

“… 93 In 2021, a randomized controlled 1-1 clinical trial under registration NCT04701710 was conducted to prioritize health personnel infected with SARS-CoV-2 (n = 232) at Argentina's Public Healthcare Centre, using the same iota-carrageenan and ivermectin regimen as in the previous study. 94 The result indicated that the number of subjects diagnosed with COVID-19 was significantly lower in the treated group, at 3.4%, than in the control group, at 21.4% (p = 0.0001). 94 The treated group also had a lower prevalence of mild to moderate COVID-19 presentation compared to the control group.…”

“… 94 The result indicated that the number of subjects diagnosed with COVID-19 was significantly lower in the treated group, at 3.4%, than in the control group, at 21.4% (p = 0.0001). 94 The treated group also had a lower prevalence of mild to moderate COVID-19 presentation compared to the control group. 94 This intensive preventive treatment with iota-carrageenan and ivermectin was able to significantly reduce the number of infected health care workers.…”

“… 94 This intensive preventive treatment with iota-carrageenan and ivermectin was able to significantly reduce the number of infected health care workers. 94 The study using iota-carrageenan in a single dose is still ongoing under the register numbers NCT04793984, NCT04681001, and NCT04590365. Therefore, the results of these ongoing clinical trials are required to provide conclusive evidence of iota-carrageenan's efficacy in patients with COVID-19.…”