The Safety of Paxlovid in Hemodialysis Patients With Covid-19 (SPHPS)

The Safety of Paxlovid (Nirmatrelvir/Ritonavir) in Hemodialysis Patients With SARS-CoV-2 Infection

Infection with SARS-CoV-2 continue to threaten global health. Persons with chronic kidney disease, including dialysis treatment are at hight risk for severe Covid-19 and associated adverse outcomes. Paxlovid (Nirmatrelvir/Ritonavir) decreases risk of progression to severe Covid-19. It is not recommended for dialysis patients because due to lack of data. The aim of the present study is evaluate the safety of Paxlovid in hemodialysis patients with SARS-CoV-2 infection.

This is a prospective study. In stage 1 arm, 10 hemodialysis patients with SARS-COV-2 infection will be treated with nirmatrelvir 150mg qd (another 75mg will be supplied after hemodialysis treatment) and ritonavir 100mg bid everyday for 5 days. In stage 2 arm, 10 patients will be treated with nirmatrelvir 300mg qd (another 150mg will be supplied after hemodialysis treatment) and ritonavir 100 bid everyday for 5 days. The primary outcome is the number of patients whose ALT, AST or total bilirubin increase two times from baseline. The secondary outcome is the number of patients whose SARS-CoV-2 lower than 500 copies/mL.

Study Overview

• Status: Completed
• Conditions: Safety Issues
• Intervention / Treatment: Drug: Nirmatrelvir and ritonavir stage 1; Drug: Nirmatrelvir and ritonavir stage 2

Detailed Description

This is a prospective, two arms (two stage) study. There will be include 20 subjects. The including criteria are 1.Understand the present study/Agree and sign informed consent; 2. Age is between 18 and 75 men or women at the screening; 3.Blood purification twice or three times/week, including hemodialysis, hemofiltration, hemodiafiltration, CRRT or hybrid blood purification; 4.Regular hemodialysis≥1 month; 5.Patients with arteriovenous fistula or artificial arteriovenous fistula; 6. Patients infected with SARS-CoV-2 and the CT value of nucleic acid detection<35. The exclusion criteria are 1.Blood purification treatment<1month; 2.Liver function (ALT or AST) is three times the upper the normal; 3.The severe or critical patients with Covid-19; 4.Patients who are treated with medicines that highly dependent on CYP3A, including but not limit to afzosin, pethidine, ranolazine, amiodarone, propafenone, quinidine, fusidic acid, voriconazole, terfenadine, colchicine, rifabutin, clozapine, dihydroergot, cisapride, simvastatin, diazepam, salbutam, triazolam, carbamazepine, phenobarbital, rifampicin; 5.Patients with galactose intolerance; 6. Pregnant and lactating women; 7.Patients was allergic to paxlovid; 8.Participating in other intervention studies; 9.The investigator judged that the condition of the subjects was not suitable for the study.

Subjects in stage 1 arm will be treated with nirmatrelvir 150mg qd (another 75mg will be supplied after hemodialysis treatment) and ritonavir 100mg bid everyday for 5 days. In stage 2 arm subjects will be treated with nirmatrelvir 300mg qd (another 150mg will be supplied after hemodialysis treatment) and ritonavir 100 bid everyday for 5 days. All of subjects will received hemodialysis two times during the study.

The primary outcome is the number of patients whose ALT, AST or total bilirubin increase two times from baseline. The secondary outcome is the number of patients whose SARS-CoV-2 lower than 500 copies/mL.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Department of Nephrology, Renji Hospital, Shanghai JiaoTong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1.Understand the present study/Agree and sign informed consent.
• 2.Age is between 18 and 75 at the screening
• 3.Blood purification twice or three times/week, including hemodialysis, hemofiltration, hemodiafiltration, CRRT or hybrid blood purification.
• 4.Regular hemodialysis≥1 month
• 5.Patients with arteriovenous fistula or artificial arteriovenous fistula.
• 6.Patients infected with Covid-19, the PCR CT value of nucleic acid detection<35.

Exclusion Criteria:

• 1.Blood purification treatment<1month.
• 2.Liver function (ALT or AST) is three times the upper the normal.
• 3.The severe or critical patients with Covid-19.
• 4.Drug that highly dependent on CYP3A, including but not limit to afzosin, pethidine, ranolazine, amiodarone, propafenone, quinidine, fusidic acid, voriconazole, terfenadine, colchicine, rifabutin, clozapine, dihydroergot, cisapride, simvastatin, diazepam, salbutam, triazolam, carbamazepine, phenobarbital, rifampicin.
• 5.Patients with galactose intolerance.
• 6. Pregnant and lactating women.
• 7.Patients was allergic to paxlovid.
• 8.Participating in other intervention studies.
• 9.The investigator judged that the condition of the subjects was not suitable for the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paxlovid stage 1 group; Subjects in stage 1 will be treated with nirmatrelvir 150mg qd (another 75mg will be supplied after hemodialysis treatment) and ritonavir 100mg bid everyday for 5 days.	Drug: Nirmatrelvir and ritonavir stage 1; Nirmatrelvir 150mg qd (another 75mg will be supplied after hemodialysis treatment) and ritonavir 100mg bid everyday for 5 days.; Other Names: small dose
Experimental: Paxlovid stage 2 group; In stage 2, subjects will be treated with nirmatrelvir 300mg qd (another 150mg will be supplied after hemodialysis treatment) and ritonavir 100 bid everyday for 5 days.	Drug: Nirmatrelvir and ritonavir stage 2; Nirmatrelvir 300mg qd (another 150mg will be supplied after hemodialysis treatment) and ritonavir 100 bid everyday for 5 days.; Other Names: high dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Liver function	Number of patients whose ALT, AST or total bilirubin increase 2 times from baseline	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effectiveness of Paxlovid	Number of patients whose SARS-CoV-2 lower than 500copies/mL	5 days

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Principal Investigator: Leyi Gu, Renal Division, Renji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2022
• Primary Completion (Actual): June 6, 2022
• Study Completion (Actual): June 8, 2022

Study Registration Dates

• First Submitted: April 28, 2022
• First Submitted That Met QC Criteria: May 6, 2022
• First Posted (Actual): May 9, 2022

Study Record Updates

• Last Update Posted (Actual): June 14, 2022
• Last Update Submitted That Met QC Criteria: June 12, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir
• Other Study ID Numbers: IIT-2022-0067

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: When the study is complete, the clinical study report will be shared.
• IPD Sharing Time Frame: September, 2022
• IPD Sharing Access Criteria: Publication
• IPD Sharing Supporting Information Type: Clinical Study Report (CSR)

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.: Yes