Clinical trial NCT05938140: Efficiency and Safety of Paxlovid for COVID-19 Patients With Severe Chronic Kidney Disease
Official title: Efficiency and Safety of Paxlovid for the Treatment of COVID-19 Patients With Severe Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: COVID-19
Renal Insufficiency, Chronic
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2023-07-10
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a prospective, single-center, open and self-controlled study.The purpose of this study is to evaluate the efficacy and safety of Paxlovid for the treatment of COVID-19 patients with severe chronic kidney disease.

Detailed description: Patients with chronic kidney disease (CKD) have a significantly increased risk of hospitalization or death due to severe COVID-19. A meta-analysis of 348 studies (382,407 COVID-19 and 1,139,979 patients with chronic kidney disease) showed that the incidence of COVID-19 in patients receiving maintenance dialysis was higher than that in CKD patients who did not need renal replacement therapy. The mortality of CKD patients in COVID-19 is higher than that of CKD patients without COVID-19. Another meta-analysis showed that COVID-19 infection was closely related to the mortality of CKD patients. The mortality rate of CKD patients infected with COVID-19 is 5.81 times higher than that of CKD patients not infected with COVID-19.

The severe/critical high-risk groups defined in the novel coronavirus Infection Diagnosis and Treatment Program formulated by the National Health and Wellness Commission include kidney disease and maintenance dialysis patients. It is clearly stated in the treatment plan that adult patients with mild or moderate severity and high risk factors should be treated with antiviral therapy within 5 days of onset.

Naimatevir tablets/ritonavir tablets (Paxlovid) are commonly used antiviral drugs at present, but it is not recommended for patients with severe renal insufficiency at present, mainly because the data of drug metabolism of Naimatevir/Ritonavir in this population are insufficient. Because the efficacy of Naimatevir/Ritonavir in patients with Covid-19 infection is clear, and the small sample of clinical research data of patients with severe renal insufficiency shows that it has a small safety risk, this study intends to carry out the safety and efficacy study of Naimatevir/Ritonavir in CKD5 patients, and at the same time, carry out the pharmacokinetic study to determine whether Naimatevir/Ritonavir can be used in the treatment of CKD5 patients.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years old
* Patients with chronic kidney disease above stage 4 (eGFR \<30ml/min/1.73m2)
* with positive DNA test or antigen test for COVID-19
* Agree to participate in the study and sign the informed consent form voluntarily

Exclusion Criteria:

* Allergic to any component of nimatevir/ritonavir tablets.
* Drugs that are being or need to be taken that are prohibited to be combined with nimatevir tablets or ritonavir tablets as specified in the instructions (including, but not limited to: methidine, amiodarone, propafenone, quinidine, simvastatin, voriconazole, fusidic acid, rifabutine, rifampicin, colchicine, clozapine, quinoline) thiopine, cisapride, simvastatin, dixima, surazadine, fluoxam, oral midazolam and triazolam etc.)
* Renal transplantation failure is taking an immune agent that namatavir tablets/ritonavir tablets can not combine.
* Severe liver injury (Child-Pugh C) or acute liver failure.
* Critically ill patients requiring ventilator-assisted respiratory support.
* patients who cannot take the whole tablet.
* HIV infection with a viral load greater than 400 copies/ml.
* Suspected or confirmed active systemic infections, other than coronavirus pneumonia, that may have an impact on the evaluation of the study.
* Uremia-related complications include acute heart failure, respiratory failure, severe chronic kidney disease, and cardiovascular disease.
* Patients who are pregnant or are planning a recent pregnancy.
* The researchers didn't consider the patients to be eligible for the study.

Primary outcomes:
measure: Security indexes
timeFrame: Start medication until 14 days
Secondary outcomes:
measure: SARS-CoV-2 nucleic acid negative transformation time
timeFrame: Start medication until 14 days
measure: The proportion of disease that progresses to severe or critical type
timeFrame: Start medication until 14 days
measure: Overall mortality from SARS-CO-2 infection
timeFrame: Start medication until 14 days
measure: Plotting the concentration-time curve of Paxlovid and its semi-logarithmic curve
timeFrame: Start medication until 14 days
measure: PK/PD scatter plots
timeFrame: Start medication until 14 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
Study officials:
affiliation: Chinese PLA General Hospital
name: Nan Bai, phD
role: STUDY_DIRECTOR
References: