Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT05364333
Other study ID # 2020-1240
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date June 1, 2022
Est. completion date April 30, 2024

Study information

Verified date April 2024
Source Heinrich-Heine University, Duesseldorf
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 40
Est. completion date April 30, 2024
Est. primary completion date April 30, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Procedure:
Remote ischemic preconditioning
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

Locations

Country Name City State
Germany University Hospital Duesseldorf Duesseldorf NRW

Sponsors (1)

Lead Sponsor Collaborator
Heinrich-Heine University, Duesseldorf

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary postoperative TIMP2-IGFBP7 concentration change in postoperative TIMP2-IGFBP7 concentration measured in urine of patients first 48 hours after HTX (arrival ICU, 24 hours after HTX, 48 hours after HTX)
Secondary Postoperative urinary biomarker concentration change in postoperative biomarker (NGAL, KIM-1, DKK3) concentration first 48 hours after HTX (arrival ICU, 24 hours after HTX, 48 hours after HTX)
Secondary AKI and renal replacement therapy early AKI or need for renalreplacement therapy first 72 hours
Secondary Major adverse kidney events (MAKE) MAKE = death, renal replacement therapy, worsened kidney function during 30 days after HTX
Secondary Major adverse cardiovascular events (MACE) MACE = cardiac death, stroke, non fatal myocardial infarction, new arrhythmia, deterioration due to congestive heart failure during 30 days after HTX
Secondary Days alive and out of hospital days spent alive and out of the hospital during 30 days after HTX
See also
  Status Clinical Trial Phase
Not yet recruiting NCT06035991 - First Clinical Evaluation of Heart Transplantation With Grafts Preserved Using an Ex-vivo Extended Perfusion System N/A
Recruiting NCT01927614 - Advanced Cardiac Imaging in Cardiac Allograft Vasculopathy N/A
Recruiting NCT01705015 - Organ Transplantation Rehabilitation: Effect of Bedside Exercise Device and Activity Reinforcement N/A
Completed NCT01655563 - Pharmacogenetic Trial of Tacrolimus After Pediatric Transplantation Phase 2
Completed NCT01028599 - Effect of Physical Training on Oxygen Uptake and Endothelial Function in Heart Transplant Recipients N/A
Completed NCT00531921 - Effects of Donor and Recipient Genetic Expression on Heart, Lung, Liver, or Kidney Transplant Survival N/A
Terminated NCT00420537 - Shift to Everolimus (RAD) Kidney Sparing Study Phase 4
Enrolling by invitation NCT03292861 - The Effect and Safety Profile of Thymoglobulin® in Primary Cardiac Transplant Recipients Phase 2
Recruiting NCT04924491 - Cell Therapy With Treg Cells Obtained From Thymic Tissue (thyTreg) to Prevent Rejection in Heart Transplant Children Phase 1/Phase 2
Recruiting NCT05270902 - Haemoadsorption During Heart Transplantation N/A
Completed NCT05289180 - Brachial Right Ventricle - Endomyocardial Biopsy
Recruiting NCT03687723 - Observational Study of the Clinical Use of the OCS™ Heart
Completed NCT01091194 - Effect of Exercise After Heart Transplantation Phase 2
Terminated NCT00678002 - Quality of Life in Pediatric Transplant Patients
Withdrawn NCT00780637 - Brachial Artery t-PA Release in Heart Transplant Recipients N/A
Withdrawn NCT00780377 - Intracoronary Bradykinin Mediated t-PA Release in Heart Transplant Recipients N/A
Completed NCT01182571 - Exploration of Fatigue, Uncertainty, Depression and Quality of Life in Heart Transplantation Recipients N/A
Terminated NCT00121784 - Heart Spare the Nephron (STN) Study - A Study of CellCept (Mycophenolate Mofetil) and Rapamune (Sirolimus) in Heart Transplant Recipients Phase 4
Withdrawn NCT00572286 - Non-invasive Evaluation of Heart Transplant Rejection- Pilot Study N/A
Completed NCT00123331 - Rapamycin Use in Calcineurin Inhibitor (CNI)-Free Immunosuppression for Stabilization/Improvement of Renal Function After Heart Transplantation Phase 4