Segurança e tolerabilidade da sotagliflozina entre receptores de transplante renal (START)
This is an investigator-initiated, randomized controlled trial in adult KTRs (N=50) with stable allograft function to assess: 1) the reversibility of the expected acute changes in eGFR with sotagliflozin (donated by Lexicon); 2) proportion of patients completing the protocol according to different eGFR reporting strategies (using a predefined algorithm to manage the expected pharmacological effect of sotagliflozin on eGFR); 3) safety and tolerability of sotagliflozin.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
-
-
Massachusetts
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Boston, Massachusetts, Estados Unidos, 02115
- Brigham and Women's
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
-
Adults ≥18 years
-
Recipients of kidney transplant with stable eGFR*
-
eGFR-creatinine (CKD-EPI 2021) ≥25 mL/min/1.73 m2
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Informed consent
- Stable eGFR will be ascertained by careful chart review establishing that the patient's current graft has been functioning for at least 12 months post-transplantation, patients have not been treated for acute rejection within the prior 3 months, and a creatinine-based eGFR is stable (two consecutive measurements separated by at least 28 days within 5 mL/min/1.73 m2) and ≥25 mL/min/1.73 m2.
Exclusion Criteria:
- Recurrent urinary tract infections (>2 episodes/year or antibiotic prophylaxis)
- Biopsy-proven acute rejection within 12 weeks
- Screening serum potassium >5.5 mmol/L
- Uncontrolled hypertension (systolic blood pressure >180/100 mmHg)
- New York Heart Association (NYHA) Class IV HF
- Myocardial infarction, unstable angina, revascularization procedure (e.g., stent or bypass graft surgery), or cerebrovascular accident within 12 weeks
- History of diabetic ketoacidosis
- Type 1 Diabetes Mellitus
- Hereditary glucose-galactose malabsorption or primary renal glucosuria
- Liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis); Alanine aminotransferase (ALT) levels >2.0 times the upper limit of normal (ULN) or total bilirubin >1.5 times the ULN, unless consistent with Gilbert's disease
- Malignancy within 5 years (exceptions: squamous and basal cell carcinomas of the skin and carcinoma of the cervix in situ, or a malignancy that in the opinion of the investigator is considered cured with minimal risk of recurrence)
- Human immunodeficiency virus antibody positive
- Major surgery within 12 weeks
- Atraumatic amputation within past 12 months of screening, or an active skin ulcer, osteomyelitis, gangrene, or critical ischemia of the lower extremity within 6 months of screening
- Combination use of ACEi and ARB
- Current use of an SGLT2 inhibitor (within 12 weeks prior to randomization)
- Known allergies, hypersensitivity, or intolerance to SGLT2i or its excipients
- Digoxin plasma level >1.2 ng/mL
- Clofibrate, fenofibrate, dronedarone, or ranolazine treatment that has not been at a stable dose in the 30 days prior to screening or randomization, or a dose adjustment is expected
- Received an active investigational drug (including vaccines) other than a placebo agent, or used an investigational medical device within 12 weeks before Day 1/baseline
- Pregnant or breast-feeding or planning to become pregnant or breast-feed during the study
- Women of childbearing potential not willing to use a highly-effective method(s) of birth control, or who are unwilling or unable to be tested for pregnancy
- Any condition that in the opinion of the investigator would make participation not in the best interest of the subject
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Patients and providers only aware of study eGFR values more than 25% below baseline
Any study-related eGFR value more than 25% below the baseline measurement will be reported to the patient and treating physician. |
To test the proportion of patients successfully completing the protocol according to different eGFR reporting strategies, randomization in a 1:1 fashion at the patient level (n=50) will occur as follows:
|
|
Outro: Patients and providers aware of all study eGFR values
All study-related eGFR measurements will be reported to the treating physician and patient. |
To test the proportion of patients successfully completing the protocol according to different eGFR reporting strategies, randomization in a 1:1 fashion at the patient level (n=50) will occur as follows:
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Reversibility of eGFR Changes
Prazo: 16 weeks total
|
Following 12 weeks of open-label drug treatment, participants will stop drug and be followed for a further four weeks (16 weeks total). Reversibility will be assessed as the proportion of patients who return to baseline eGFR (+/- 10%) by the end of the 4-week off-treatment period. |
16 weeks total
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Proportion of Patients Successfully Completing the Full Treatment Protocol, According to Randomized Groups
Prazo: 16 weeks total
|
Following 12 weeks of open-label drug treatment, participants will stop drug and be followed for a further four weeks. The proportion of patients completing the full 16 weeks will be compared according to randomized groups. |
16 weeks total
|
Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Safety Assessments
Prazo: 4 weeks
|
- Acute changes in eGFR (baseline to 4 weeks) |
4 weeks
|
|
Safety Assessments
Prazo: 12 weeks
|
- Longer-term changes in eGFR (baseline to 12 weeks and 4 weeks to 12 weeks) |
12 weeks
|
|
Safety Assessments
Prazo: Weeks 12-16 (off-drug)
|
- Reversibility of changes in eGFR (12 to 16 weeks - after drug discontinuation) |
Weeks 12-16 (off-drug)
|
|
Safety Assessments
Prazo: 12 weeks
|
- Acute Kidney Injury (>50% increase in serum creatinine/40% decline in eGFR within one week), which will be assessed throughout the on-drug period of 12 weeks |
12 weeks
|
|
Safety Assessments
Prazo: 12 weeks
|
- All adverse events (AEs) |
12 weeks
|
|
Safety Assessments
Prazo: 12 weeks
|
- All serious adverse events (SAEs) |
12 weeks
|
|
Safety Assessments
Prazo: 12 weeks
|
- Diarrhea |
12 weeks
|
|
Safety Assessments
Prazo: 12 weeks
|
- Infection requiring treatment with anti-microbials (including urogenital infection and urinary tract infections) |
12 weeks
|
|
Safety Assessments
Prazo: 12 weeks
|
- Severe hypoglycemia (event that requires assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions) |
12 weeks
|
|
Safety Assessments
Prazo: 12 weeks
|
- Diabetic ketoacidosis |
12 weeks
|
|
Safety Assessments
Prazo: 12 weeks
|
- Hyperkalemia (>5.5 mmol/L) |
12 weeks
|
|
Safety Assessments
Prazo: 12 weeks
|
- Hypotension (symptomatic SBP <90 mmHg or hypotension requiring adjustment in blood pressure medications or treatment in an emergency or hospitalized setting) |
12 weeks
|
|
Tolerability Assessments
Prazo: 12 weeks
|
- Proportion of participants able to complete the full 12 weeks of treatment, according to randomized arm |
12 weeks
|
|
Tolerability Assessments
Prazo: 12 weeks
|
- Study medication discontinuation rates |
12 weeks
|
|
Tolerability Assessments
Prazo: 12 weeks
|
- KDQOL-36 questionnaire |
12 weeks
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Martina M McGrath, MBBCh, Brigham and Women's Hospital
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Real)
Conclusão do estudo (Real)
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
Outros números de identificação do estudo
- 2022P000454
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Only sharing of anonymized data will be considered as per approved protocol. Written requests for data sharing will be considered on a case-by-case basis from qualified external researchers, based on scientific merit.
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