Early Treatment With Ivermectin and LosarTAN for Cancer Patients With COVID-19 Infection

Study Overview
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Brief Summary
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Ivermectin plus losartan as prophilaxy to severe events in patients with cancer with recent diagnosis of COVID-19

Detailed Description
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This is a randomized, doubled-blind and placebo-controlled phase II study that will evaluate the efficacy of the early use of ivermectin plus losartan in cancer patients who present with recent diagnosis of COVID-19. The trial will enroll 176 patients with previous diagnosis of active cancer (88 in each arm) and the aim of the study is to assess the efficacy of these drugs combination to decrease the incidence of COVID-19 severe complications. Patients will receive single dose ivermectin of 12mg after the confirmed diagnosis of COVID-19, followed by 15 days of losartan. We believe that the association of anti-viral activity of the ivermectin plus the extracellular blockade of the receptor used by the virus will decrease the overall viremia and subsequently improve clinical outcomes.

Official Title
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Randomized, Doubled-blind Phase II Trial Evaluating the Use of Ivermectin Plus Losartan for Prophylaxis of Severe Events in Cancer Patients With Recent Diagnosis of COVID-19

Conditions
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Cancer, COVID, Coronavirus Infection

Intervention / Treatment
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* Drug: Placebo
* Drug: Ivermectin
* Drug: Losartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to 18 years of age Ability to understand and sign informed consent Biopsy-proven diagnosis of previous cancer (solid or hematologic disease) Participants must be diagnosed with active malignancy, defined as the presence of metastatic disease; or patient undergoing curative treatment during cancer treatment, regardless of the therapeutic modality. Confirmed diagnosis of COVID-19 by the presence of a positive PCR test or positive serological test and / or diagnosis presumed by the presence of flu-like symptoms associated to suggestive findings on CT scan. ECOG performance status 0 to 2 Patients must have an assessment of adequate organ function within 28 days prior to enrollment, evidenced by: Hemoglobin ≥ 9.0 g / dL Leukometry> 2,000 / mm3 Absolute neutrophil count ≥ 1,500 / mm3 Platelet count ≥ 100,000 / mm3 Creatinine clearance ≥ 30 mL / min. Creatinine clearance (CrCl) should be calculated according to the Cockcroft-Gault formula. Total bilirubin <3 x the upper limit of normal (ULN), except for patients with known Gilbert's syndrome. Aspartate aminotransaminase (AST) <3.0 x LSN. Alanine aminotransaminase (ALT) <3.0 x ULN. Exclusion Criteria: Currently taking an angiotensin converting enzyme inhibitor (ACEi) or Angiotensin receptor blocker (ARB). Patients who presents with severe conditions at the time of diagnosis requiring ICU admission. Prior reaction or intolerance to an ARB or ACE inhibitor. Blood pressure less than 110/70 mmHg at presentation Potassium greater than 5.0 mEq / L Pregnancy or breastfeeding Prior reaction to Ivermectin. Patient currently enrolled in another research protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: ARM A: Placebo<br>Patients will receive ivermectin-placebo single dose on the day of confirmed diagnosis of COVID-19, followed by losartan-placebo daily for 15 days. | Drug: Placebo<br>* Use of the combination of ivermectin-placebo plus losartan-placebo as early treatment for COVID-19 in cancer patients<br>|
| Experimental: ARM B: Ivermectin plus losartan<br>Patients will receive a single dose of 12mg of ivermectin on the day of the confirmed diagnosis of COVID-19, followed by losartan 50mg orally once daily for 15 consecutive days | Drug: Ivermectin<br>* Use of the combination of ivermectin plus losartan as early treatment for COVID-19 in cancer patients<br>Drug: Losartan<br>* Use of the combination of ivermectin plus losartan as early treatment for COVID-19 in cancer patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of severe complications due COVID-19 infection | Incidence of severe complications due COVID-19 infection defined as need for ICU admission, need for mechanical ventilation, or death | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Severe Acute Respiratory Syndrome | Severe Acute Respiratory Syndrome defined as oxygen saturation less than 93% | 28 days | 
| Incidence of Severe Acute Respiratory Syndrome | Severe Acute Respiratory Syndrome defined as respiratory rate higher than 24 incursion per minute | 28 days | 
| Adverse events | Incidence of hepatic toxicity (elevation of ALT, AST above the upper limit of normal, measured by U/L) | 28 days | 
| Adverse events | Incidence of hepatic toxicity (elevation of bilirubin above the upper limit of normal, measured by mg/dL) | 28 days | 
| Adverse events | Incidence of renal toxicity (elevation of serum creatinine levels above the upper limit of normal, measured by mg/dL) | 28 days | 
| Adverse events | Incidence of symptomatic postural hypotension, diagnosed by clinical assessment of reduction of > 20 mmHG of arterial systolic pressure after measurement in prone position and orthostatic position. | 28 days | 
| Overall survival | Death of any cause since protocol enrollment | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, covid-19, losartan, ivermectin