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Remote Ischemic Preconditioning and Acute Kidney Injury in HTX (RIPCAT)

Primary Purpose

Heart Transplantation

Status
Recruiting
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Remote ischemic preconditioning
Sponsored by
Heinrich-Heine University, Duesseldorf
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Transplantation focused on measuring orthotopic heart transplantation, HTX

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

- adult patients (>18 years) undergoing HTX

Exclusion Criteria:

  • Acute myocardial infarction up to 7 days before surgery
  • age younger than 18 years
  • pre-existing AKI
  • previous kidney transplantation
  • chronic kidney disease with a glomerular filtration rate less than 30ml/min
  • pregnancy
  • peripheral vascular disease affecting the upper limbs
  • hepato-renal syndrome
  • drug therapy with sulfonamide or nicorandil

Sites / Locations

  • University Hospital DuesseldorfRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Sham Comparator

Experimental

Arm Label

Sham RIPC

RIPC

Arm Description

Control patients will be submitted to 3 cycles of sham RIPC. Each cycle of Sham RIPC consists of a pseudo ischemia of the left upper limb caused by inflating a blood pressure cuff to 20mmHg for 5 minutes followed by 5 minutes of reperfusion time.

Patients in the intervention group will be submitted to 3 cycles of RIPC. For each cycle of RIPC, a blood pressure cuff will be inflated at 200mmHg for 5 minutes (or at least 50mmHg above the systolic arterial blood pressure) followed by 5 minutes of reperfusion time.

Outcomes

Primary Outcome Measures

postoperative TIMP2-IGFBP7 concentration
change in postoperative TIMP2-IGFBP7 concentration measured in urine of patients

Secondary Outcome Measures

Postoperative urinary biomarker concentration
change in postoperative biomarker (NGAL, KIM-1, DKK3) concentration
AKI and renal replacement therapy
early AKI or need for renalreplacement therapy
Major adverse kidney events (MAKE)
MAKE = death, renal replacement therapy, worsened kidney function
Major adverse cardiovascular events (MACE)
MACE = cardiac death, stroke, non fatal myocardial infarction, new arrhythmia, deterioration due to congestive heart failure
Days alive and out of hospital
days spent alive and out of the hospital

Full Information

First Posted
May 4, 2022
Last Updated
June 20, 2022
Sponsor
Heinrich-Heine University, Duesseldorf
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1. Study Identification

Unique Protocol Identification Number
NCT05364333
Brief Title
Remote Ischemic Preconditioning and Acute Kidney Injury in HTX
Acronym
RIPCAT
Official Title
Effect of Remote Ischemic Preconditioning on Acute Kidney Injury in Patients Undergoing Heart Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2022 (Actual)
Primary Completion Date
June 1, 2024 (Anticipated)
Study Completion Date
July 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Heinrich-Heine University, Duesseldorf

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Postoperative Acute Kidney Injury (AKI) is a common complication after heart transplantation (HTX) affecting outcome of patients. Remote ischemic preconditioning (RIPC) is an intervention that showed positive effect on incidence of AKI in elective cardiac surgery. Effects of RIPC on AKI in HTX patients have not been investigated to date. Recently new biomarkers have been established, showing high sensitivity and specificity for AKI. Especially, Insulin-Like Growth Factor Binding Protein 7 (IGFBP7) together with Tissue Inhibitor of Metalloproteinases-2 (TIMP-2), known as nephrocheck®, are diagnostic biomarkers in this context. Hence, the investigators want to conduct a randomized controlled feasibility and proof of concept trial to determine the effects of RIPC on AKI after HTX, defined/detected using postoperative urinary [TIMP-2]*[IGFBP-7] concentration.
Detailed Description
Postoperative Acute Kidney Injury (AKI) is a common complication after heart transplantation (HTX) affecting outcome of patients. Anesthesia- and surgery-related factors, but also hemodynamic instability and nephrotoxic drugs are triggering AKI and are frequent in HTX patients. A recent meta-analysis showed that incidences of AKI (according to KDIGO criteria) and AKI requiring renal replacement therapy (RRT) after HTX are 62.8% and 11.8% respectively. Crucially, AKI post HTX is associated with reduced short term and 1-year patient survival as well as long-term outcome. Impaired baseline renal function due to heart failure is a main risk factor for AKI in patients undergoing heart transplant surgery. Our recent data shows that postoperative AKI requiring RRT is also frequent in patients with adequate baseline renal function after HTX. Again, nephrotoxicity of immunosuppressive drugs and treatment of hemodynamic instability by vasopressors showed relevance in risk prediction of AKI. Due to the high incidence of AKI and its strong effect on patient outcome and with regard to the increasing cases of end stage heart failure and Heart transplant surgery in recent years, AKI prevention holds promise to relevant outcome improvement in the future. However, recommended interventions to prevent AKI, i.e. avoidance of nephrotoxic drugs, improvement of hemodynamics or fluid therapy are limited in this specific setting. Thus, it is of big interest to identify procedures which could reduce AKI after HTX. Remote ischemic preconditioning (RIPC) has been suggested in this context and the effects of RIPC on AKI have been investigated by several studies in the cardiac surgery setting. RIPC achieves ischemic preconditioning by non-invasive repetitive induction of limb ischemia blood pressure cuff. Thus, it is an intervention with barely relevant adverse effects. Moreover, RIPC is an investigator-independent and cost-effective procedure. Zarbock et al. showed in a randomized clinical trial (RCT) that RIPC compared with no RIPC significantly reduced the rate of AKI and use of RRT in 240 patients undergoing on-pump coronary artery bypass graft (CABG) or valvular surgery. Although these results could be replicated by another single center RIPC trial, other RCTs could not show effects of RIPC on AKI. However, a recent meta-analysis of randomized controlled trials shows favorable effects of RIPC on incidence of AKI in patients undergoing cardiac surgery. Referring to the lack of alternatives, the high incidence of AKI and its deleterious long-term sequelae, RIPC is worth to be investigated as a promising strategy for renal protection after HTX. Of note, previous results from studies in the CABG or valvular surgery setting cannot be translated to patients undergoing HTX. Although cardiopulmonary bypass (CPB) is used in all of these patients, the hemodynamic situation after CPB can be different in patients with or without HTX when extracorporeal life support systems are used. Recently new biomarkers have been established, showing high sensitivity and specificity for AKI. Especially, Insulin-Like Growth Factor Binding Protein 7 (IGFBP7) together with Tissue Inhibitor of Metalloproteinases-2 (TIMP-2), known as nephrocheck®, are diagnostic biomarkers in this context. Both intracellular proteins are released during tubular epithelial stress, as present during AKI. Those markers may help to better understand the effects of RIPC on AKI. To date there are no RCTs investigating the effects of RIPC on postoperative AKI in this specific population of HTX patients. Hence, the investigators want to conduct a randomized controlled feasibility and proof of concept trial to determine the effects of RIPC on AKI after HTX, defined/detected using urinary [TIMP-2]*[IGFBP-7] concentration. Moreover, the investigators will analyze the impact of RIPC on renal and cardiac function as well as other important clinical outcomes as secondary endpoints. If this feasibility and proof-of-concept trial will have a positive result in terms of 1) the effect of the intervention and 2) the feasibility of our study design, the investigators will conduct a pragmatic multicenter RCT to answer the question if RIPC can really improve outcome of patients undergoing HTX.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Transplantation
Keywords
orthotopic heart transplantation, HTX

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
38 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sham RIPC
Arm Type
Sham Comparator
Arm Description
Control patients will be submitted to 3 cycles of sham RIPC. Each cycle of Sham RIPC consists of a pseudo ischemia of the left upper limb caused by inflating a blood pressure cuff to 20mmHg for 5 minutes followed by 5 minutes of reperfusion time.
Arm Title
RIPC
Arm Type
Experimental
Arm Description
Patients in the intervention group will be submitted to 3 cycles of RIPC. For each cycle of RIPC, a blood pressure cuff will be inflated at 200mmHg for 5 minutes (or at least 50mmHg above the systolic arterial blood pressure) followed by 5 minutes of reperfusion time.
Intervention Type
Procedure
Intervention Name(s)
Remote ischemic preconditioning
Intervention Description
For each cycle of RIPC, a blood pressure cuff will be inflated to the non-dominant arm at 200mmHg for 5 minutes (or at least 50mmHg above the systolic arterial blood pressure) followed by 5 minutes of reperfusion time
Primary Outcome Measure Information:
Title
postoperative TIMP2-IGFBP7 concentration
Description
change in postoperative TIMP2-IGFBP7 concentration measured in urine of patients
Time Frame
first 48 hours after HTX (arrival ICU, 24 hours after HTX, 48 hours after HTX)
Secondary Outcome Measure Information:
Title
Postoperative urinary biomarker concentration
Description
change in postoperative biomarker (NGAL, KIM-1, DKK3) concentration
Time Frame
first 48 hours after HTX (arrival ICU, 24 hours after HTX, 48 hours after HTX)
Title
AKI and renal replacement therapy
Description
early AKI or need for renalreplacement therapy
Time Frame
first 72 hours
Title
Major adverse kidney events (MAKE)
Description
MAKE = death, renal replacement therapy, worsened kidney function
Time Frame
during 30 days after HTX
Title
Major adverse cardiovascular events (MACE)
Description
MACE = cardiac death, stroke, non fatal myocardial infarction, new arrhythmia, deterioration due to congestive heart failure
Time Frame
during 30 days after HTX
Title
Days alive and out of hospital
Description
days spent alive and out of the hospital
Time Frame
during 30 days after HTX

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - adult patients (>18 years) undergoing HTX Exclusion Criteria: Acute myocardial infarction up to 7 days before surgery age younger than 18 years pre-existing AKI previous kidney transplantation chronic kidney disease with a glomerular filtration rate less than 30ml/min pregnancy peripheral vascular disease affecting the upper limbs hepato-renal syndrome drug therapy with sulfonamide or nicorandil
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
René M'Pembele, MD
Phone
+492118118451
Email
rene.mpembele@med.uni-duesseldorf.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
René M'Pembele, M.D.
Organizational Affiliation
Heinrich-Heine University, Duesseldorf
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Duesseldorf
City
Duesseldorf
State/Province
NRW
ZIP/Postal Code
40225
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
René M'Pembele, MD
Phone
+4902118118451
Email
rene.mpembele@med.uni-duesseldorf.de

12. IPD Sharing Statement

Plan to Share IPD
No

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Remote Ischemic Preconditioning and Acute Kidney Injury in HTX

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