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- Ensaio Clínico NCT07672860
Perioperative Ursodeoxycholic Acid for Renal Protection in Adults Undergoing Partial Nephrectomy for Renal Tumors (PURIFY)
Protective Effect of Perioperative Ursodeoxycholic Acid Intervention Against Ischemia-Reperfusion Injury During Partial Nephrectomy: A Single-Center, Prospective, Double-Blind, Randomized Controlled Trial (PURIFY Trial)
The goal of this clinical trial is to learn if ursodeoxycholic acid, also called UDCA, can help protect kidney function in adults undergoing partial nephrectomy for kidney tumors. It will also learn about the safety of UDCA when used around the time of surgery.
Before the randomized part of the study begins, the first 6 participants will receive UDCA in a safety run-in phase. These participants will be closely monitored for side effects, laboratory abnormalities, and other medical problems to assess the preliminary safety and tolerability of perioperative UDCA administration. If no unacceptable safety concerns are identified, the study will proceed to the randomized, placebo-controlled phase.
The main questions this study aims to answer are:
- Is perioperative UDCA administration safe in patients undergoing surgery for renal tumors?
- Does UDCA lower the risk of acute kidney injury within 48 hours after partial nephrectomy?
- Does UDCA reduce the decline in kidney function after surgery?
- Does UDCA increase blood levels of UDCA and related bile acids during the perioperative period?
- What medical problems do participants have when taking UDCA around the time of surgery?
- Researchers will also evaluate whether UDCA affects urinary biomarkers of kidney injury.
Researchers will compare UDCA with a placebo, a look-alike substance that contains no active drug, to see if UDCA can help protect the kidney from ischemia-reperfusion injury during partial nephrectomy.
Participants will:
- Take UDCA or a placebo three times a day from 2 days before surgery until 5 days after surgery.
- Undergo partial nephrectomy as planned by their treating surgeon.
- Have blood tests before and after surgery to check kidney function, liver function, and bile acid levels.
- Participants will provide urine samples before and after surgery for the assessment of kidney injury biomarkers.
- Be monitored for side effects, surgical complications, and other medical problems during hospitalization and follow-up.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
Partial nephrectomy (PN) is the preferred nephron-sparing surgical approach for T1 renal tumors, providing oncological outcomes comparable to those of radical nephrectomy while better preserving renal function. However, temporary renal artery clamping during PN may induce renal ischemia-reperfusion injury (IRI), thereby increasing the risk of postoperative acute kidney injury and long-term renal functional decline. Currently, no pharmacological intervention has been proven to provide definitive and effective perioperative renal protection in patients undergoing PN. Ursodeoxycholic acid (UDCA), an endogenous bile acid, has a well-established safety profile and good clinical accessibility. Previous studies in experimental models of kidney injury have shown that UDCA may exert renoprotective effects through mechanisms including amelioration of mitochondrial dysfunction, attenuation of oxidative stress and inflammatory responses, and improvement of impaired fatty acid oxidation.
This study aims to evaluate whether perioperative administration of UDCA can attenuate renal injury caused by ischemia-reperfusion during PN. In addition, by monitoring renal function, liver function, bile acid levels, and relevant kidney injury biomarkers, this study will comprehensively assess the efficacy and safety of perioperative UDCA administration, thereby providing evidence for its potential application in perioperative renal protection in kidney surgery.
Before the randomized phase begins, the first six enrolled patients will receive UDCA treatment and will be observed and evaluated as part of a safety run-in phase. Participants in this phase will be included in the safety analysis but will not be included in the final efficacy analysis of the randomized phase. If no unacceptable safety risks are identified during the safety run-in phase, the study will proceed to the randomized, double-blind, placebo-controlled phase.
After completion of the safety analysis, investigators will screen all patients scheduled to undergo PN at the time of hospital admission. Patients who meet the eligibility criteria and voluntarily agree to participate in the study will be randomized after providing written informed consent.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
Contactos e Locais
Contato de estudo
- Nome: Qu Le M.D
- Número de telefone: +86 15720625951
- E-mail: septsoul@hotmail.com
Locais de estudo
-
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Jiangsu
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Nanjing, Jiangsu, China, 210000
- Recrutamento
- Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing
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Contato:
- Qu Le M.D
- Número de telefone: +86 15720625951
- E-mail: septsoul@hotmail.com
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
1. Inclusion Criteria
Patients must meet all of the following criteria to be eligible for inclusion in the study:
- The patient has fully understood the study and has voluntarily signed the informed consent form (ICF);
- Male or female patients aged 18 to 75 years, inclusive, at the time of signing the ICF;
- Imaging diagnosis consistent with stage T1 renal tumor, as assessed by MRI or CT;
- No definite collecting system invasion on preoperative MRI or CT assessment;
- The patient is scheduled to undergo partial nephrectomy (PN) or renal tumor enucleation after clinical evaluation by the physician and full discussion with the patient;
- Preoperative assessment indicates that main renal artery clamping with warm ischemia is planned;
- The surgery will be performed by a surgeon with experience in at least 50 cases of PN or renal tumor enucleation, and renal artery clamping will be performed using standardized vascular clamp application;
- Screening eGFR ≥30 mL/min/1.73 m², calculated using the CKD-EPI equation;
- No history of allergy or intolerance to UDCA or other bile acid preparations, and no UDCA contraindications or biliary tract-related diseases that, in the investigator's judgment, would make the patient unsuitable for UDCA treatment;
- The subject is willing and able to comply with the scheduled visits, treatment, laboratory tests, and other study-related procedures required by the protocol.
2. Exclusion Criteria
Patients meeting any of the following criteria will be excluded from the study:
- Emergency surgery, defined as surgery required for medical reasons within 24 hours;
- Patients who are considered preoperatively to have a significant risk of bleeding, or whose surgery is expected to require complex renal reconstruction, and who are judged by the investigator to be unsuitable for participation in this study;
- Patients for whom non-standard ischemia techniques, such as selective/segmental arterial clamping or zero-ischemia techniques, are planned preoperatively;
- Patients with a history of renal surgery on either kidney or previous kidney transplantation;
- Solitary kidney;
- History of major abdominal organ surgery within 1 year before surgery, which, in the investigator's judgment, may affect the conduct of the current surgery, safety assessment, or evaluation of study endpoints;
- Active lesions or clinically significant imaging abnormalities in either kidney that may substantially affect renal function assessment or perioperative AKI risk evaluation, including but not limited to renal artery stenosis, polycystic kidney disease, chronic pyelonephritis, severe hydronephrosis, or renal atrophy;
- Use of UDCA, chenodeoxycholic acid, bile acid sequestrants, or other drugs that may significantly affect bile acid metabolism within 1 month before screening;
- Continuous or systemic use of nephrotoxic drugs for more than 1 week within 3 months before screening, including but not limited to nonsteroidal anti-inflammatory drugs and aminoglycoside antibiotics;
- Continuous or systemic use of drugs that may significantly affect the gut microbiota or bile acid metabolism within 1 month before screening, including antibiotics, probiotics, high-dose glucocorticoids, immunosuppressants, potent laxatives, or antidiarrheal agents;
- Participation in another interventional clinical study within 3 months before screening, or ongoing treatment with another investigational drug or device;
- Uncontrolled active infection during the screening period, including but not limited to urinary tract infection, pulmonary infection, intra-abdominal infection, or systemic infection;
- Uncontrolled blood pressure abnormalities during the screening period, including mean seated SBP ≥180 mmHg or DBP ≥110 mmHg; symptomatic hypotension, SBP <90 mmHg, or hypovolemia as judged by the investigator;
- History of New York Heart Association (NYHA) class III-IV heart failure, or hospitalization due to heart failure/fluid retention within 6 months before screening;
- Hepatic impairment, defined as meeting any of the following criteria: history of hepatic encephalopathy, history of esophagogastric varices, history of portocaval shunt surgery, Child-Pugh class C hepatic impairment, ALT or AST >3 × ULN, or total bilirubin >2 × ULN during the screening period;
- Diseases or surgical history that may significantly affect the absorption, distribution, metabolism, or excretion of the study drug, including but not limited to:
1. history of active inflammatory bowel disease within the previous 6 months; 2. history of major gastrointestinal surgery, such as gastrectomy, gastrointestinal anastomosis, or bowel resection; 3. history of gastrointestinal ulcer and/or gastrointestinal or rectal bleeding within the previous 6 months; 4. history of pancreatic injury or pancreatitis within the previous 6 months; (17) Pregnant or breastfeeding women; (18) Women of childbearing potential who have a positive pregnancy test during the screening period, or who are unwilling to use effective contraception during the study; (19) Patients with a history of other malignancies are excluded, except for malignancies confirmed to have been cured or in remission for ≥5 years, radically resected basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ at any site; (20) Any other severe or uncontrolled medical disease, psychiatric disorder, or laboratory abnormality that may increase the risk associated with study participation, affect subject compliance, or interfere with the interpretation of study results, including but not limited to organ failure, active or uncontrolled immunodeficiency disease, active or uncontrolled HBV/HCV/HIV infection, cognitive impairment, or severe psychiatric disorder.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: UDCA
Participants will receive UDCA (250 mg, tid)
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Ursodeoxycholic Acid Capsules 250 mg, 1 capsule tid.
UDCA will be administered orally three times daily, starting 2 days before surgery and continuing through postoperative day 5.
|
|
Comparador de Placebo: placebo
Participants will receive placebo(1 capsule tid)
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1 capsule tid.
Placebo will be administered orally three times daily, starting 2 days before surgery and continuing through postoperative day 5.
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Incidence of AKI within 48 hours after surgery
Prazo: From baseline to 48 hours after surgery.
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Defined according to the serum creatinine criterion of the KDIGO criteria
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From baseline to 48 hours after surgery.
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Incidence of AKI within 48 hours after surgery(Defined according to either the serum creatinine or urine output criterion of the KDIGO criteria)
Prazo: From baseline to 48 hours after surgery.
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Defined according to either the serum creatinine or urine output criterion of the KDIGO criteria
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From baseline to 48 hours after surgery.
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Between-group difference in mean eGFR on postoperative day 1
Prazo: From baseline to 24 hours after surgery.
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This endpoint will be assessed using an analysis of covariance model
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From baseline to 24 hours after surgery.
|
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Between-group difference in mean eGFR on postoperative day 2
Prazo: From baseline to 48 hours after surgery.
|
This endpoint will be assessed using an analysis of covariance model
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From baseline to 48 hours after surgery.
|
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Maximum absolute increase in serum creatinine from baseline within 48 hours after surgery
Prazo: From baseline to 48 hours after surgery.
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Maximum absolute increase = highest postoperative serum creatinine within 48 hours - baseline serum creatinine
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From baseline to 48 hours after surgery.
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Perioperative complications
Prazo: Perioperatively
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Assessed according to the Clavien-Dindo classification
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Perioperatively
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UDCA-related adverse events
Prazo: From the first administration of the study drug until 7 days after the last administration.
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Including gastrointestinal reactions, hepatobiliary abnormalities, skin reactions, and allergic reactions
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From the first administration of the study drug until 7 days after the last administration.
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Change From Baseline in ALT and AST Levels
Prazo: Perioperatively
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Change from baseline in ALT and AST levels will be calculated as the ALT or AST value at postoperative assessment time point minus the corresponding baseline value.
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Perioperatively
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Between-group difference in mean affected-kidney eGFR at 6 months after surgery
Prazo: at 6 months after surgery
|
This endpoint will be assessed using an analysis of covariance model.
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at 6 months after surgery
|
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Acute Ipsilateral Renal Dysfunction spectrum score (AIRD)
Prazo: at 6 months after surgery
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at 6 months after surgery
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|
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Ischemia Recovery Index (IRI)
Prazo: at 6 months after surgery
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at 6 months after surgery
|
|
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Affected-kidney eGFR recovery rate
Prazo: at 6 months after surgery
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at 6 months after surgery
|
|
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Incidence of a ≥25% decline from baseline in eGFR within 1 year after surgery
Prazo: Baseline to 1 year after surgery
|
Baseline to 1 year after surgery
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Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Change from baseline in serum UDCA concentration
Prazo: Perioperatively
|
Change from baseline to postoperative day 1
|
Perioperatively
|
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Perioperative changes in urinary NGAL biomarker levels
Prazo: Perioperatively
|
Change from baseline to postoperative day 1
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Perioperatively
|
Colaboradores e Investigadores
Patrocinador
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças urogenitais
- Doenças Vasculares
- Doenças cardiovasculares
- Complicações pós-operatórias
- Processos Patológicos
- Neoplasias urogenitais
- Neoplasias por local
- Neoplasias
- Doenças Urogenitais Masculinas
- Doenças renais
- Doenças Urológicas
- Doenças Urogenitais Femininas
- Doenças urogenitais femininas e complicações na gravidez
- Insuficiência renal
- Neoplasias Urológicas
- Condições Patológicas, Sinais e Sintomas
- Lesão Renal Aguda
- Neoplasias Renais
- Lesão de Reperfusão
- Compostos policíclicos
- Esteróides
- Compostos de anel fundido
- Ácido desoxicólico
- Ácidos cólicos
- Ácidos biliares e sais
- CHOLANES
- Ácido Ursodesoxicólico
Outros números de identificação do estudo
- 2025DZKY-180-02
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
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