Nephrospec Switzerland

Official title

Low-intensity Extracorporeal Shockwave Therapy With the Nephrospec TM Device for the Treatment of Hypertension in Patients Diagnosed With Chronic Kidney Disease (CKD) : a Randomized, Double-blind Sham-controlled Monocentric Trial

Overview

This is a randomized, double-blind sham-controlled monocentric trial. 30 patients that are diagnosed with hypertension and with moderate to severe chronic kidney disease are included in this trial. 20 of them are randomized into the active treatment arm, 10 into the sham arm. Low-intensity extracorporal shock wave (Li-ESWT) sessions (arm1) or sham sessions (arm2), will be administered with a dedicated probe within three consecutive weeks to the kidneys of patients.The study will add data to the effects of the shock wave treatment on blood pressure and will assess whether this treatment improves renal function, perfusion and oxygenation. The study includes a third arm (arm3) in which treatment sessions are administered to patients that were in the placebo group in the first phase of the study (arm2).

Detailed description

This is a randomized, double-blind sham-controlled monocentric trial. Adult patients that are diagnosed with hypertension (systolic blood pressure 135 - 180 mmHg), currently on stable (over 60 days) medical therapy and with moderate to severe chronic kidney disease (eGFR 20-70 mL/min/1.73m2) or with eGFR between 60-90 ml/min/1.73m 2 and albuminuria ≥30 mg/mmol in spot urine or ≥300 mg/day in 24h urine collection who are currently on stable (at least 60 days) medical therapy are included in this trial.

20 patients are randomized into the active treatment arm with the investigational medical device, 10 patients into the sham arm. Low-intensity extracorporal shock wave (Li-ESWT) sessions (arm1) with a dedicated probe (Nephrospec device) or sham sessions (arm2), within three consecutive weeks, will be applied to the kidneys of patients. Patients will be followed-up for 48 weeks after the treatment.The study includes a third arm (arm3) in which treatment sessions are administered to patients that were in the placebo group in the first phase of the study and for whom their condition did not improve (arm 2).

Low-intensity extracorporeal shockwave therapy (Li-ESWT) is based on the classic technique of lithotripsy for the extracorporeal treatment of kidney stones but applied at much lower intensity (\~10%). Previous histological studies in animals have shown that Li-ESWT has favourable effects on kidney perfusion and oxygenation. In human studies that included patients with diabetic nephropathy, six to twelve sessions of Li-ESWT lead to long-term reduction of blood pressure and stabilization of renal function (eGFR). The medical device Nephrospec TM is CE-mark and used in the ambulatory setting to lower BP in patients with CKD. The device will be used according to the instructions and indications mentioned in the operator manual.

The primary outcome of this trial is the change in systolic 24-hour ambulatory blood pressure (ABPM) from baseline to 12 weeks post treatment. Further important secondary ouctomes are automatic office blood pressure (AOBP), the change in number or dose of blood pressure medications, the change in eGFR and the change in albumine/creatinine ratio (ACR). Furthermore, the study will assess whether the treatment improves renal function, Contrast enhanced ultrasound (CEUS)-assessed perfusion index, as well as renal oxygenation and fibrosis (ADC) assessed by MRI.

Interventions

• Device NephrospecTM, low-intensity extracorporal shockwave therapy device
  Patients will receive 6 Li-ESWT treatments with the NephrospecTM device over three consecutive weeks, with a minimal recess of 24 hours between treatments and a maximum of 3 sessions per week. Three hundred shockwaves will be applied by the PI or co-PI to each one of 8 pre-selected regions of each kidney, under ultrasound control, with the patient in the prone position. No local anaesthesia is needed. Total treatment time of one session is 30 minutes. The participant will remain under supervisi
• Device Sham-Device
  The sham device is the NephrospecTM applicator with an internal barrier to prevent shockwaves to pass through to the patient.

Primary outcome measures

• Systolic 24-hour ambulatory blood pressure (ABPM) [Time frame: Baseline to 12-weeks (-1/+3weeks) Follow-up post last treatment.]

Secondary outcome measures (10)

• attended Automatic Office Blood Pressure [Time frame: baseline to 4 weeks (+3 weeks), 24 weeks (±3 weeks) and 48 weeks (±3 weeks) post last treatment]
• unattended Automatic Office Blood Pressure [Time frame: from baseline to 4 weeks (+3 weeks), 24 weeks (±3 weeks) and 48 weeks (±3 weeks) post last treatment]
• Number, dose or number of medications to maintain blood pressure control [Time frame: baseline to 24 weeks (±3 weeks), and 48 weeks (±3 weeks) post last treatment]
• Serum creatinine levels / eGFR - calculated by CKD - EPI [Time frame: baseline to 4 weeks (+3 weeks), 12 weeks (-1/+3 weeks), 24 weeks (±3 weeks), and 48 weeks (±3 weeks) post last treatment.]
• Albumin/creatinine ratio (ACR) [Time frame: baseline to 4 weeks (+3 weeks), 12 weeks (-1/+3 weeks), 24 weeks (±3 weeks), and 48 weeks (±3 weeks) post last treatment.]
• CEUS-assessed Perfusion Index (PI) [Time frame: baseline to 12 weeks (±3 weeks)]
• MRI-assessed oxygenation (R2*), fibrosis (ADC) and Phase-contrast [Time frame: baseline to 12 weeks (±3 weeks)]
• Plasma renin activity [Time frame: baseline to 12 weeks (±3 weeks)]
• Plasma aldosterone levels [Time frame: baseline to 12 weeks (±3 weeks)]
• Cystatin C levels [Time frame: baseline to 12 weeks (±3 weeks)]

Eligibility criteria

Inclusion criteria

• Age: 18 years to 82 years.
• Patient is diagnosed with Hypertension, i.e. home,office and/or 24h systolic blood pressure ≥135 mmHg (as per ISH guidelines, 2020), currently on stable (over 60 days) medical therapy as prescribed by a physician, of none, one, or more antihypertensive medication classes. Patients will be considered stable if no relevant medication change for over 60 days or for 30 days if there were no previous changes 90 days before the current change.
• Patients diagnosed with moderate to severe chronic renal failure (eGFR 20-70 mL/min/1.73m2) who are currently on stable medical therapy as prescribed by a physician.
• Patients with eGFR between 60-90 ml/min/1.73m2 and albuminuria >=30mg/mmol in spot urine or >=300mg/day in 24h urine collection
• Patient is able and willing to comply with the required follow-up schedule.
• Patient is capable of giving an informed consent.

Exclusion criteria

• Hypertension: Individual's systolic BP is over 180mmHg when receiving stable medical medication regimen as prescribed by a physician, of none, one, or more antihypertensive medication classes at maximally tolerated dose. Hypertension secondary to an identifiable and treatable cause, other than Renal artery stenosis or CKD, or is prescribed a medication that may raise BP.
• History of previous renal artery stent. Stent or other intervention involving renal arteries including but not limited to renal denervation procedures.
• Kidney conditions non compatible with the study: Patient has an eGFR <20 ml/min/1.73m², is on Dialysis or has had a kidney transplant performed. Active pyelonephritis. History of or current kidney stones. Patients with polycystic kidney disease or a known complicated renal cyst (Bosniak III or higher).
• Symptomatic patients (Macrohematuria) with a decrease of over 2 grams in Hb.
• Hemoglobin (Hb) ≤ 9 grams per deciliter (blood).
• Coagulation issues: Bleeding tendency resulting from hematologic disease. Subjects having INR > 2.5 and PT, PTT and platelet count which deviates from the clinical laboratory normal reference range.
• Diseases non compatible with the study: Recent (less than 6 months) history of myocardial infarction, PCI, stroke or hospitalization for HFrEF (heart failure with reduced ejection fraction). Individual has type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus (HbA1c > 10%).
• Active Cancer - primary tumor or metastatic, such as liver, renal, testicular, abdominal tumor or local tumor at treatment area..
• Treatment non compatible with the study: Patients that have been treated with immunosuppression in the last 3 months. Individual requires chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnea. No change in dosing of RAS inhibitors in the month prior to the procedure is required.
• Technical impossibility to participate: Local infection of the skin at the area to be in contact with the applicator.
• Known allergy to Sonovue® contrast product (hypersensibility to sulfur hexyfluoride or another component).
• No other contraindication to SonoVue, ie. patients with right-to-left shunts, severe pulmonary hypertension (pulmonary arterial pressure > 90 mm Hg), uncontrolled systemic hypertension and in adult patients with respiratory distress syndrome (ARDS).
• Contraindication to undergo MR-imaging such as the presence of a pacemaker or other implanted metallic device or severe claustrophobia.
• Inability to follow the procedures of the investigation, e.g. due to language problems, psychological disorders, dementia, etc. of the subject/ Unable to obtain consent
• Known or suspected non-compliance, drug or alcohol abuse
• Individual works night shifts.
• Individual is pregnant, breast feeding or planning to become pregnant.
• Individual does not want to be informed in case of accidental finding related to individual's health discovered during imaging or other study-related exams.
• Participation in another investigation with an investigational drug or another MD within the 30 days preceding and during the present investigation,
• Previous enrolment into the current investigation,
• Enrolment of the PI, his/her family members, employees, and other dependent persons

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Switzerland · 1 center

• Department of Nephrology, Centre Hospitalier Universitaire Vaudois — Lausanne

Identifiers

NCT: NCT06194591 · 2023-D0075

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗