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

Primary Purpose

Cancer, COVID, Coronavirus Infection

Status
Terminated
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Placebo
Ivermectin
Losartan
Sponsored by
Instituto do Cancer do Estado de São Paulo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer focused on measuring cancer, covid-19, losartan, ivermectin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Instituto do Cancer do Estado de Sao Paulo

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

ARM A: Placebo

ARM B: Ivermectin plus losartan

Arm Description

Patients will receive ivermectin-placebo single dose on the day of confirmed diagnosis of COVID-19, followed by losartan-placebo daily for 15 days.

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Incidence of Severe Acute Respiratory Syndrome
Severe Acute Respiratory Syndrome defined as oxygen saturation less than 93%
Incidence of Severe Acute Respiratory Syndrome
Severe Acute Respiratory Syndrome defined as respiratory rate higher than 24 incursion per minute
Adverse events
Incidence of hepatic toxicity (elevation of ALT, AST above the upper limit of normal, measured by U/L)
Adverse events
Incidence of hepatic toxicity (elevation of bilirubin above the upper limit of normal, measured by mg/dL)
Adverse events
Incidence of renal toxicity (elevation of serum creatinine levels above the upper limit of normal, measured by mg/dL)
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.
Overall survival
Death of any cause since protocol enrollment

Full Information

First Posted
June 22, 2020
Last Updated
August 5, 2022
Sponsor
Instituto do Cancer do Estado de São Paulo
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1. Study Identification

Unique Protocol Identification Number
NCT04447235
Brief Title
Early Treatment With Ivermectin and LosarTAN for Cancer Patients With COVID-19 Infection
Acronym
TITAN
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Terminated
Why Stopped
futility analysis has demonstrated no difference between arms
Study Start Date
July 23, 2020 (Actual)
Primary Completion Date
June 30, 2022 (Actual)
Study Completion Date
June 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Instituto do Cancer do Estado de São Paulo

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, COVID, Coronavirus Infection
Keywords
cancer, covid-19, losartan, ivermectin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Masking Description
doubled-blind and placebo-controlled
Allocation
Randomized
Enrollment
77 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ARM A: Placebo
Arm Type
Placebo Comparator
Arm Description
Patients will receive ivermectin-placebo single dose on the day of confirmed diagnosis of COVID-19, followed by losartan-placebo daily for 15 days.
Arm Title
ARM B: Ivermectin plus losartan
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Use of the combination of ivermectin-placebo plus losartan-placebo as early treatment for COVID-19 in cancer patients
Intervention Type
Drug
Intervention Name(s)
Ivermectin
Intervention Description
Use of the combination of ivermectin plus losartan as early treatment for COVID-19 in cancer patients
Intervention Type
Drug
Intervention Name(s)
Losartan
Intervention Description
Use of the combination of ivermectin plus losartan as early treatment for COVID-19 in cancer patients
Primary Outcome Measure Information:
Title
Incidence of severe complications due COVID-19 infection
Description
Incidence of severe complications due COVID-19 infection defined as need for ICU admission, need for mechanical ventilation, or death
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Incidence of Severe Acute Respiratory Syndrome
Description
Severe Acute Respiratory Syndrome defined as oxygen saturation less than 93%
Time Frame
28 days
Title
Incidence of Severe Acute Respiratory Syndrome
Description
Severe Acute Respiratory Syndrome defined as respiratory rate higher than 24 incursion per minute
Time Frame
28 days
Title
Adverse events
Description
Incidence of hepatic toxicity (elevation of ALT, AST above the upper limit of normal, measured by U/L)
Time Frame
28 days
Title
Adverse events
Description
Incidence of hepatic toxicity (elevation of bilirubin above the upper limit of normal, measured by mg/dL)
Time Frame
28 days
Title
Adverse events
Description
Incidence of renal toxicity (elevation of serum creatinine levels above the upper limit of normal, measured by mg/dL)
Time Frame
28 days
Title
Adverse events
Description
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.
Time Frame
28 days
Title
Overall survival
Description
Death of any cause since protocol enrollment
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pedro Exman, MD
Organizational Affiliation
Instituto do Cancer do Estado de São Paulo
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Maria del Pilar Diz, MD, PhD
Organizational Affiliation
Instituto do Cancer do Estado de São Paulo
Official's Role
Study Director
Facility Information:
Facility Name
Instituto do Cancer do Estado de Sao Paulo
City
SAo Paulo
ZIP/Postal Code
01246-000
Country
Brazil

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
no plan to share individual participant data

Learn more about this trial

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

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