The Safety of Paxlovid in Hemodialysis Patients With Covid-19

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Safety Issues

Intervention / Treatment
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* Drug: Nirmatrelvir and ritonavir stage 1
* Drug: Nirmatrelvir and ritonavir stage 2


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paxlovid stage 1 group<br>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<br>* Nirmatrelvir 150mg qd (another 75mg will be supplied after hemodialysis treatment) and ritonavir 100mg bid everyday for 5 days.<br>* Other names: small dose;|
| Experimental: Paxlovid stage 2 group<br>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<br>* Nirmatrelvir 300mg qd (another 150mg will be supplied after hemodialysis treatment) and ritonavir 100 bid everyday for 5 days.<br>* Other names: high dose;|

What is the study measuring?
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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 |