Innocuité et tolérance de la sotagliflozine chez les receveurs de greffe rénale (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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Réel)
Phase
- Phase 2
Contacts et emplacements
Lieux d'étude
-
-
Massachusetts
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Boston, Massachusetts, États-Unis, 02115
- Brigham and Women's
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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:
|
|
Autre: 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:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Reversibility of eGFR Changes
Délai: 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
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Proportion of Patients Successfully Completing the Full Treatment Protocol, According to Randomized Groups
Délai: 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
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Safety Assessments
Délai: 4 weeks
|
- Acute changes in eGFR (baseline to 4 weeks) |
4 weeks
|
|
Safety Assessments
Délai: 12 weeks
|
- Longer-term changes in eGFR (baseline to 12 weeks and 4 weeks to 12 weeks) |
12 weeks
|
|
Safety Assessments
Délai: Weeks 12-16 (off-drug)
|
- Reversibility of changes in eGFR (12 to 16 weeks - after drug discontinuation) |
Weeks 12-16 (off-drug)
|
|
Safety Assessments
Délai: 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
Délai: 12 weeks
|
- All adverse events (AEs) |
12 weeks
|
|
Safety Assessments
Délai: 12 weeks
|
- All serious adverse events (SAEs) |
12 weeks
|
|
Safety Assessments
Délai: 12 weeks
|
- Diarrhea |
12 weeks
|
|
Safety Assessments
Délai: 12 weeks
|
- Infection requiring treatment with anti-microbials (including urogenital infection and urinary tract infections) |
12 weeks
|
|
Safety Assessments
Délai: 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
Délai: 12 weeks
|
- Diabetic ketoacidosis |
12 weeks
|
|
Safety Assessments
Délai: 12 weeks
|
- Hyperkalemia (>5.5 mmol/L) |
12 weeks
|
|
Safety Assessments
Délai: 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
Délai: 12 weeks
|
- Proportion of participants able to complete the full 12 weeks of treatment, according to randomized arm |
12 weeks
|
|
Tolerability Assessments
Délai: 12 weeks
|
- Study medication discontinuation rates |
12 weeks
|
|
Tolerability Assessments
Délai: 12 weeks
|
- KDQOL-36 questionnaire |
12 weeks
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Martina M McGrath, MBBCh, Brigham and Women's Hospital
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Autres numéros d'identification d'étude
- 2022P000454
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime 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.
Informations sur les médicaments et les dispositifs, documents d'étude
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