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

• ClinicalTrials.gov Identifier: NCT04447235
• Recruitment Status: Terminated
• First Posted: June 25, 2020
• Last Update Posted: August 9, 2022
• Sponsor: Instituto do Cancer do Estado de São Paulo
• Information provided by (Responsible Party): Instituto do Cancer do Estado de São Paulo

Tracking Information

• First Submitted Date: June 22, 2020
• First Posted Date: June 25, 2020
• Last Update Posted Date: August 9, 2022
• Actual Study Start Date: July 23, 2020
• Actual Primary Completion Date: June 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 23, 2020)

Incidence of severe complications due COVID-19 infection [ Time Frame: 28 days ]

Incidence of severe complications due COVID-19 infection defined as need for ICU admission, need for mechanical ventilation, or death

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 23, 2020)

• Incidence of Severe Acute Respiratory Syndrome [ Time Frame: 28 days ]
  Severe Acute Respiratory Syndrome defined as oxygen saturation less than 93%
• Incidence of Severe Acute Respiratory Syndrome [ Time Frame: 28 days ]
  Severe Acute Respiratory Syndrome defined as respiratory rate higher than 24 incursion per minute
• Adverse events [ Time Frame: 28 days ]
  Incidence of hepatic toxicity (elevation of ALT, AST above the upper limit of normal, measured by U/L)
• Adverse events [ Time Frame: 28 days ]
  Incidence of hepatic toxicity (elevation of bilirubin above the upper limit of normal, measured by mg/dL)
• Adverse events [ Time Frame: 28 days ]
  Incidence of renal toxicity (elevation of serum creatinine levels above the upper limit of normal, measured by mg/dL)
• Adverse events [ Time Frame: 28 days ]
  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 [ Time Frame: 28 days ]
  Death of any cause since protocol enrollment

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Early Treatment With Ivermectin and LosarTAN for Cancer Patients With COVID-19 Infection
• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Masking Description:

doubled-blind and placebo-controlled

Primary Purpose: Treatment

Condition

• Cancer
• COVID
• Coronavirus Infection

Intervention

• Drug: Placebo
  Use of the combination of ivermectin-placebo plus losartan-placebo as early treatment for COVID-19 in cancer patients
• 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

Study Arms

• 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.
  Intervention: Drug: Placebo
• 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
  Interventions:

  • Drug: Ivermectin
  • Drug: Losartan

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: August 5, 2022): 77
• Original Estimated Enrollment (submitted: June 23, 2020): 176
• Actual Study Completion Date: June 30, 2022
• Actual Primary Completion Date: June 30, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT04447235
• Other Study ID Numbers: NP 1677/20
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

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

• Current Responsible Party: Instituto do Cancer do Estado de São Paulo
• Original Responsible Party: Same as current
• Current Study Sponsor: Instituto do Cancer do Estado de São Paulo
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Instituto do Cancer do Estado de São Paulo
• Verification Date: August 2022