Reducing Hypoxia in Patients With Coronavirus Disease (COVID-19) Using Topotecan With Standard of Care

• Status: Recruiting
• Trial end date: 2022-03-31
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of the phase 1 trial is to identify a dose of topotecan that will be safe to take forward into a Phase 2 trial, with no unexpected toxicities or drug-drug interactions with standard therapy for COVID-19. The investigators hypothesise that a single dose of low-dose Topotecan will blunt the expression of inflammatory genes in patients with moderate COVID-19, without cytotoxic side effects.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National University Hospital, Singapore
• Collaborator: Christian Medical College, Vellore, India
• Treatments: Topotecan

Criteria

Inclusion Criteria:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by at least 1 positive Polymerase Chain Reaction (PCR) test

• Moderate COVID as evidenced by Oxygen saturation <93% on room air (or <88% if prior CLD)

• Admission to emergency department for monitoring and/or supportive care:

• The following biochemical markers:

• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. Platelets ≥ 100 x 109/L, Haemoglobin ≥ 9x 109/L.

• Bilirubin < 1.5 times upper limit of normal (ULN). Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) < 2.5 times ULN.

• Calculated creatinine clearance of ≥ 30ml/min calculated using the formula of Cockcroft and Gault: (140-age) x mass (kg)/)72x creatinine mg/dl); multiple by 0.85 if female.

• Laboratory features of cytokine release, as defined by any 1 of the following:

i. C-reactive protein (CRP)> 75mg/L ii. Lactate Dehydrogenase (LDH) > ULN iii. D-dimer > 1.0 mg/L iv. Ferritin > 500ng/ml v. Elevated Interleukin-6 levels

Exclusion Criteria:

• Patients requiring mechanical ventilation

• Any immunosuppressive medication including chemotherapy(excluding steroids) administered concurrently or within last 14 days.

• Patients with uncontrolled diabetes mellitus (HbA1C within 1 month >8)

• Pregnancy or Breastfeeding.

• Known allergy to Topotecan. Unconjugated hyperbilirubinemia on a fasting Liver Function Test (LFT), which can indicate Gilberts Syndrome.

• Suspected active bacterial, fungal, or other infection in addition to COVID-19.

• Any condition that would, in the opinion of the Investigator, increase the risk of the participant

• by participating in the study.

• Inability to provide consent.

• Unable to comply with study procedures.