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

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

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

Study Overview

• Status: Terminated
• Conditions: Coronavirus Infection; Cancer; COVID
• Intervention / Treatment: Drug: Placebo; Drug: Ivermectin; Drug: Losartan

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • SAo Paulo, Brazil, 01246-000
    • Instituto do Cancer do Estado de Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: ARM A: Placebo; 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; Use of the combination of ivermectin-placebo plus losartan-placebo as early treatment for COVID-19 in cancer patients
Experimental: ARM B: Ivermectin plus losartan; 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; Use of the combination of ivermectin plus losartan as early treatment for COVID-19 in cancer patients; Drug: Losartan; Use of the combination of ivermectin plus losartan as early treatment for COVID-19 in cancer patients

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Instituto do Cancer do Estado de São Paulo
• Investigators: Principal Investigator: Pedro Exman, MD, Instituto do Cancer do Estado de Sao Paulo; Study Director: Maria del Pilar Diz, MD, PhD, Instituto do Cancer do Estado de Sao Paulo

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2020
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: June 22, 2020
• First Submitted That Met QC Criteria: June 23, 2020
• First Posted (Actual): June 25, 2020

Study Record Updates

• Last Update Posted (Actual): August 9, 2022
• Last Update Submitted That Met QC Criteria: August 5, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: cancer; covid-19; losartan; ivermectin
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Infections; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Anti-Infective Agents; Antiparasitic Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan; Ivermectin
• Other Study ID Numbers: NP 1677/20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: no plan to share individual participant data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No