Sotagliflozin sicurezza e tollerabilità tra i destinatari del trapianto renale (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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
-
-
Massachusetts
-
Boston, Massachusetts, Stati Uniti, 02115
- Brigham and Women's
-
-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
-
Adults ≥18 years
-
Recipients of kidney transplant with stable eGFR*
-
eGFR-creatinine (CKD-EPI 2021) ≥25 mL/min/1.73 m2
-
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: 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:
|
|
Altro: 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:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Reversibility of eGFR Changes
Lasso di tempo: 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
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Proportion of Patients Successfully Completing the Full Treatment Protocol, According to Randomized Groups
Lasso di tempo: 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
|
Altre misure di risultato
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Safety Assessments
Lasso di tempo: 4 weeks
|
- Acute changes in eGFR (baseline to 4 weeks) |
4 weeks
|
|
Safety Assessments
Lasso di tempo: 12 weeks
|
- Longer-term changes in eGFR (baseline to 12 weeks and 4 weeks to 12 weeks) |
12 weeks
|
|
Safety Assessments
Lasso di tempo: Weeks 12-16 (off-drug)
|
- Reversibility of changes in eGFR (12 to 16 weeks - after drug discontinuation) |
Weeks 12-16 (off-drug)
|
|
Safety Assessments
Lasso di tempo: 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
Lasso di tempo: 12 weeks
|
- All adverse events (AEs) |
12 weeks
|
|
Safety Assessments
Lasso di tempo: 12 weeks
|
- All serious adverse events (SAEs) |
12 weeks
|
|
Safety Assessments
Lasso di tempo: 12 weeks
|
- Diarrhea |
12 weeks
|
|
Safety Assessments
Lasso di tempo: 12 weeks
|
- Infection requiring treatment with anti-microbials (including urogenital infection and urinary tract infections) |
12 weeks
|
|
Safety Assessments
Lasso di tempo: 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
Lasso di tempo: 12 weeks
|
- Diabetic ketoacidosis |
12 weeks
|
|
Safety Assessments
Lasso di tempo: 12 weeks
|
- Hyperkalemia (>5.5 mmol/L) |
12 weeks
|
|
Safety Assessments
Lasso di tempo: 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
Lasso di tempo: 12 weeks
|
- Proportion of participants able to complete the full 12 weeks of treatment, according to randomized arm |
12 weeks
|
|
Tolerability Assessments
Lasso di tempo: 12 weeks
|
- Study medication discontinuation rates |
12 weeks
|
|
Tolerability Assessments
Lasso di tempo: 12 weeks
|
- KDQOL-36 questionnaire |
12 weeks
|
Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: Martina M McGrath, MBBCh, Brigham and Women's Hospital
Pubblicazioni e link utili
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Altri numeri di identificazione dello studio
- 2022P000454
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano 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.
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
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