Kidney Disease and Ultrasound Imaging (Imag-NCT)

• ClinicalTrials.gov Identifier: NCT02201537
• Recruitment Status: Completed
• First Posted: July 28, 2014
• Last Update Posted: December 21, 2017
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Fondation de l'Avenir; Bracco Imaging S.p.A.
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: July 17, 2014
• First Posted Date: July 28, 2014
• Last Update Posted Date: December 21, 2017
• Actual Study Start Date: March 19, 2013
• Actual Primary Completion Date: March 19, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 18, 2014)

• renal Elastography [ Time Frame: 3 months ]
  The assessment of renal function is performed by the serum creatinine and calculation of glomerular filtration rate estimated by the formula Modified Diet in Renal Disease (MDRD) 4-parameter at 3 and 12 months post-transplantation. In addition, a measure of glomerular filtration rate using the technique to iohexol is performed routinely at 12 months post-transplant as part of routine monitoring of transplant patient. The ultrasound functional imaging will be performed at 15 days, 3 and 12 months after transplantation. The functional imaging examinations will be held as follows: Step 1: the conventional Doppler ultrasound 2nd step: the ultrasound elastography Step 3 : CEUS
• Renal Elastography and contrast-enhanced US [ Time Frame: 12 months ]
  The assessment of renal function is performed by the serum creatinine and calculation of glomerular filtration rate estimated by the formula Modified Diet in Renal Disease (MDRD) 4-parameter at 3 and 12 months post-transplantation. In addition, a measure of glomerular filtration rate using the technique to iohexol is performed routinely at 12 months post-transplant as part of routine monitoring of transplant patient. The ultrasound functional imaging will be performed at 15 days, 3 and 12 months after transplantation. The functional imaging examinations will be held as follows: Step 1: the conventional Doppler ultrasound 2nd step: the ultrasound elastography Step 3 : CEUS

Original Primary Outcome Measures (submitted: July 25, 2014)

• renal Elastography [ Time Frame: 3 months ]
  The assessment of renal function is performed by the serum creatinine and calculation of glomerular filtration rate estimated by the formula Modified Diet in Renal Disease (MDRD) 4-parameter at 3 and 12 months post-transplantation. In addition, a measure of glomerular filtration rate using the technique to iohexol is performed routinely at 12 months post-transplant as part of routine monitoring of transplant patient. The ultrasound functional imaging will be performed at 3 and 12 months after the transplant. The functional imaging examinations will be held as follows: Step 1: the conventional Doppler ultrasound 2nd step: the ultrasound elastography Step 3 : CEUS
• renal Elastography [ Time Frame: 12 months ]
  The assessment of renal function is performed by the serum creatinine and calculation of glomerular filtration rate estimated by the formula Modified Diet in Renal Disease (MDRD) 4-parameter at 3 and 12 months post-transplantation. In addition, a measure of glomerular filtration rate using the technique to iohexol is performed routinely at 12 months post-transplant as part of routine monitoring of transplant patient. The ultrasound functional imaging will be performed at 3 and 12 months after the transplant. The functional imaging examinations will be held as follows: Step 1: the conventional Doppler ultrasound 2nd step: the ultrasound elastography Step 3 : CEUS

Current Secondary Outcome Measures (submitted: November 18, 2014)

• renal Elastography [ Time Frame: 3 months ]
  Correlation between elastography and renal function with degree of fibrosis and renal function will be calculate using Pearson coefficient of correlation
• Correlation between renal elastography and perfusion and degree of fibrosis and renal function [ Time Frame: 12 months ]
  Correlation between elastography and renal function with degree of fibrosis and renal function will be calculate using Pearson coefficient of correlation
• renal Elastography in patients with chronic kidney disease [ Time Frame: 12 months ]
  this two measures will be express in evolution percentage at J15 and 3 months. The evolution percentage will be compared with imaging of patient with chronic kidney disease to determine if elastography and renal perfusion can predict chronic kidney disease at one year.

Original Secondary Outcome Measures (submitted: July 25, 2014)

• renal Elastography [ Time Frame: 3 months ]
  Correlation between elastography and renal function with degree of fibrosis and renal function will be calculate using Pearson coefficient of correlation
• Correlation between renal elastography and degree of fibrosis and renal function [ Time Frame: 12 months ]
  Correlation between elastography and renal function with degree of fibrosis and renal function will be calculate using Pearson coefficient of correlation
• renal Elastography in patients with chronic kidney disease [ Time Frame: 12 months ]
  this two measures will be express in evolution percentage at J15 and 3 months. The evolution percentage will be compared with imaging of patient with chronic kidney disease to determine if elastography and renal perfusion can predict chronic kidney disease at one year.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Kidney Disease and Ultrasound Imaging
• Official Title: Non-invasive Diagnosis of Chronic Kidney Disease in Renal Transplants Kidney Transplanted Using Ultrasound Functional Imaging
• Brief Summary: The hypothesis of our study is that a correlation exists between the couple ultrasound elastography- renal perfusion estimated with contrast-enhanced ultrasound and the degree of fibrosis estimated in a semi-quantitative way in 4 stages (0; 25 %; 25-50 %; > 50 %), as elastography alone did not allow to differentiate moderated fibrosis at 3 months in our feasibility study.

Detailed Description

Kidney transplant patients are exposed to long-term immunosuppressive therapy, and have an increased risk of infections and cancer, while a lack of treatment increases the risk of rejection. The development of imaging techniques to characterize the status of the graft remains a challenge in transplantation. Ideally, they should identify complications (acute rejection, chronic allograft nephropathy, nephrotoxicity ...) without the need for invasive procedures and thus lead to better customization of immunosuppressive therapy.

The post-transplant follow-up is based on the monitoring of graft function. Impaired function suggests the possibility of a complication, but requires confirmation by an invasive procedure such as renal biopsy. In addition, the diagnosis remains complex at a relatively advanced stage of the process due to damage to the graft parenchyma. To anticipate the altered function and detect subclinical lesions, screening biopsies have been used to diagnose chronic rejection. By definition, screening for subclinical lesions can not be based on any biological parameter; the diagnosis of subclinical complications thus requires performing multiple systematic biopsies, which are scheduled at 3 months and 1 year.

Doppler ultrasound is an imaging method of choice for the study of renal transplant, but it cannot diagnose the NCT due to the absence of specific findings. The lack of early diagnostic test for NCT is a major obstacle to the development and evaluation of new therapeutic options to prevent, slow or stabilize renal fibrosis. It is therefore necessary to develop a non-invasive imaging technique for the early diagnosis of NCT.

Ultrasound elastography is a technique that allows tissue stiffness measurements and provides a parametric picture.

The main objective of our study is to evaluate the performances of elastography and measurement of renal perfusion (area under the ROC curve) to diagnose the NCT and determine for each both measures a threshold to maximize the sensitivity. These performances will be evaluated at 3 months and 12 months. The results can also be compared to other imaging modalities such as functional MRI, and to clinical events (obstruction, infection…).

Functional ultrasound imaging should identify diagnostic and prognostic criteria of NCT, and enable the development of less invasive therapeutic protocols to evaluate new therapeutic approaches

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Screening
• Condition: Recipient of Kidney Transplant

Intervention

Device: renal echography

Renal biopsy will be performed at 3 and 12 months.

The functional imaging examinations will be held as follows:

Step 1: the conventional Doppler ultrasound Step 2: ultrasound elastography Step 3: CEUS

Study Arms

Imag-NCT

The ultrasound functional imaging will be performed at J15 (before the patient is discharged from service Transplantation) and at 3 and 12 months after the transplant.

The functional imaging examinations will be held as follows:

• 1st stage - the conventional Doppler ultrasound:
• 2nd stage - the elastography:.
• Step 3 - CEUS: It is performed on an ultrasound machine with a specific module with the same probes as conventional ultrasound. It requires the injection of 1.5 ml of SonoVue ®, a contrast ultrasound.

Renal biopsy will be performed after the functional ultrasound at 3 and 12 months.

Intervention: Device: renal echography

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 25, 2016): 141
• Original Estimated Enrollment (submitted: July 25, 2014): 160
• Actual Study Completion Date: March 19, 2016
• Actual Primary Completion Date: March 19, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age ≥ 18 years;
• Patient with informed consent;
• Recipient of a living donor graft or cadaveric donor patient;
• No contraindication for biopsy of the graft;

• No contraindication to the injection of SonoVue ®:

  • hypersensitivity to sulfur hexafluoride
  • acute coronary syndrome, unstable ischemic heart disease (myocardial infarction phase formation or evolution, typical resting angina in the previous 7 days, significant worsening of cardiac symptoms in the previous 7 days, recent intervention on the coronary arteries or another factor suggesting clinical instability (eg, recent deterioration of ECG changes in clinical or laboratory parameters), acute heart failure, stage III or IV heart failure, severe arrhythmias.
  • right-left shunt, severe pulmonary hypertension (PAP> 90 mmHg), uncontrolled systemic hypertension, respiratory distress syndrome
• Affiliated to a social security scheme

Exclusion Criteria:

• Refusal to participate in the study;
• Inability / refusal to give informed consent;
• contraindication for biopsy testing graft;
• Presence of a contraindication to the injection of SonoVue ®.
• Presence of a peripheral venous access in a non-restricted already infused patient, not pickable under ultrasound
• Breastfeeding, pregnancy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT02201537
• Other Study ID Numbers: 2012-A01070-43
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Assistance Publique - Hôpitaux de Paris
• Study Sponsor: Assistance Publique - Hôpitaux de Paris

Collaborators

• Fondation de l'Avenir
• Bracco Imaging S.p.A.

Investigators

• Principal Investigator: Jean-Michel CORREAS, PUPH; Necker Hospital

• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: December 2017