Extended Remdesivir Infusion Combined With Nirmatrelvir/Ritonavir for Persistent SARS-CoV-2 Infection in Immunocompromised Patients (SARS-CoV-2)

To evaluate the safety and efficacy of extended remdesivir infusion, targeting on immunocompromised individuals who had positive SARS-CoV-2 PCR despite an oral antiviral agent prescription.

Study Overview

• Status: Not yet recruiting
• Conditions: COVID-19; SARS-CoV-2; Immunocompromised
• Intervention / Treatment: Drug: combination therapy; Drug: SOC

Detailed Description

Prolonged viral shedding is commonly observed in immunocompromised patients infected by SARS-CoV-2. Until now, there is no successful clinical trial or guideline to guide optimal treatment for this clinical condition. Here, we aimed to establish a clinical trial with combination of prolonged remdesivir infusion with nirmatrelvir/ritonavir among COVID-19 patients recently receiving b-cell depletion therapy, to evaluate to clinical outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jann-Tay Wang, M. D., Ph.D.; Phone Number: 263517 +886-2-2312-3456; Email: wangjt1124@ntuh.gov.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, 100225
    • National Taiwan University Hospital
    • Contact: Fu-Chang Tsai, Professor; Phone Number: 288576 +886-2312-3456; Email: fctsai@ntu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Receive B-cell depletion therapy or bendamustine within 6months
• Laboratory confirmed SARS-CoV-2 infection
• Symptoms onset within 72 hours
• NIAID ordinal score 0-5 upon enrollment

Exclusion Criteria:

• Prior use of any anti-SARS-CoV-2 agents within 2 weeks. Remdesivir or NMV/r initiated within 24 hours is acceptable
• Life expectancy < 1 month
• Previous adverse effect related to remdesivir or NMV/r
• Concurrent use medicine with drug-drug interaction with NMV/r
• Patients receiving intubation and mechanical ventilation
• eGFR < 30
• Child pugh score Class C
• Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a subject participating in the trial or would render the subject unable to comply with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: combination therapy; combination of 5-day remdesivir and 10-day Nirmatrelvir/Ritonavir	Drug: combination therapy; A combination of 5-day remdesivir and 10-day Nirmatrelvir/Ritonavir; Other Names: remdesivir and Nirmatrelvir/Ritonavir; Drug: SOC; Standard of care
Active Comparator: SOC; standard of care	Drug: SOC; Standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of SARS-CoV-2 CT > 30 on Day 14	The proportion of SARS-CoV-2 CT > 30 on Day 14 of each group.	From enrollment to the end of treatment on Day 14.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of mortality or respiratory failure requiring intubation and mechanical ventilation.	The proportion of mortality or respiratory failure requiring intubation and mechanical ventilation within 28 days after antiviral agent initiation of each group.	From enrollment to the end of treatment on Day 28.
The proportion of patients developing anti-viral treatment emerging adverse events.	The proportion of patients developing anti-viral treatment emerging adverse events.	From enrollment to the end of treatment on Day 28.
The proportion of secondary bacterial or fungal infection of each group.	The proportion of secondary bacterial or fungal infection of each group.	From enrollment to the end of treatment on Day 28.
The proportion of viral rebound within 28 days after antiviral agent initiation.	The proportion of viral rebound within 28 days after antiviral agent initiation of each group.	From enrollment to the end of treatment on Day 28.

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 21, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: September 22, 2024
• First Submitted That Met QC Criteria: September 22, 2024
• First Posted (Actual): September 24, 2024

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 24, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Extended RDV infusion combination therapy for SARS-CoV-2 infection in immunocompromised patients
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Remdesivir; Nirmatrelvir; Nirmatrelvir and ritonavir drug combination
• Other Study ID Numbers: 202405064MIND

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No