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Tolvaptan-Octreotide LAR Combination in ADPKD

This study looks to examine two medications shown to effectively slow total kidney and cystic volume growth and glomerular filtration rate (GFR) decline in patients with ADPKD. The short-term effect of both medications appear to be larger when the GFR is normal or even higher than normal and kidney volumes are still relatively stable. Investigators will compare the short-term effects of Tolvaptan on its own and Tolvaptan plus Octreotide LAR combination therapy on TKV as assessed by MRI, and on GFR in ADPKD patients with normal (80 to 120 ml/min/1.73m2) kidney function or even kidney hyperfiltration (GFR ≥120 ml/min/1.73m2).

Intervention:

Drug: Tolvaptan

Drug: Octreotide LAR

Drug: Placebo

Inclusion criteria:

  • Adult (>18-yr-old) men and women, with a clinical and ultrasonographic diagnosis of ADPKD;
  • Serum creatinine < 1.0 mg/dl (for man) and < 1.2 mg/dl (for woman) and changes in serum creatinine (and creatinine clearance when available) <30% over the last six months;
  • Creatinine clearance > 80 ml/min/1.73m2 measured one to two weeks apart during the pre-screening period;
  • GFR ≥ 80 ml/min/1.73m2 (by iohexol plasma clearance technique) at screening and baseline evaluations;
  • TKV ranging between 1000 and 2000 ml at screening (by ultrasound imaging) and at baseline (by MRI) evaluations

Exclusion criteria:

  • Patients with concomitant systemic, renal parenchymal or urinary tract disease;
  • Diabetes;
  • Overt proteinuria (urinary protein excretion rate >1 g/24 hours);
  • Abnormal urinalysis suggestive of concomitant, clinically significant glomerular disease, urinary tract lithiasis, infection or obstruction, biliary tract lithiasis or obstruction;
  • Hemorrhagic or complicated cysts which might acutely affect kidney function and volumes;
  • QT-related ECG abnormalities;
  • Cancer and major systemic diseases that could prevent completion of the planned follow-up or interfere with data collection or interpretation;
  • Hypersensitivity to the IMP active substance or to any of the excipients or to benzazepine or benzazepine derivatives;
  • Concomitant treatment with drugs that may affect glomerular hemodynamics during the three months before the beginning of the study (including ACE inhibitors, angiotensin receptor blockers, aldosterone antagonists and non-steroideal anti-inflammatory medications);
  • Elevated liver enzymes and/or signs or symptoms of liver injury prior to initiation of treatment that meet the requirements for permanent discontinuation of tolvaptan
  • Patients with anuria, volume depletion and hypernatraemia
  • Patients who cannot perceive or respond to thirst
  • Ferro-magnetic prosthesis, aneurysm clips, severe claustrophobia or any other contraindication to MRI evaluation;
  • Psychiatric disorders and any condition that could prevent full comprehension of the purposes and risks of the study;
  • Pregnant or lactating;
  • Participation in another interventional clinical trial within the 4 weeks prior to screening.

 

Contact Information:

Piero Ruggenenti, MD
003903545351
piero.ruggenenti@marionegri.it

Norberto Perico, MD
0039035453531
norberto.perico@marionegri.it