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Trial record 9 of 52 for:    TIMP2

Remote Ischemic Preconditioning After Cardiac Surgery (RIPCRenal)

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ClinicalTrials.gov Identifier: NCT02997748
Recruitment Status : Recruiting
First Posted : December 20, 2016
Last Update Posted : January 30, 2018
Sponsor:
Collaborator:
Else Kröner Fresenius Foundation
Information provided by (Responsible Party):
University Hospital Muenster

Brief Summary:
Acute kidney injury (AKI) is a well-recognized complication after cardiac surgery with cardiopulmonary bypass (CPB). The aim of this study is to reduce the incidence of AKI by implementing remote ischemic preconditioning and to evaluate the dose-response relationship using the biomarkers urinary [TIMP-2] *[IGFBP7] in high risk patients undergoing cardiac surgery.

Condition or disease Intervention/treatment Phase
Cardiac Surgery, Aortocoronary Bypass Procedure: Remote ischemic preconditioning (RIPC) Not Applicable

Detailed Description:

Acute kidney injury (AKI) complicates 7-19% of cardiac surgical procedures. The investigators recently found that remote ischemic preconditioning (RIPC) using transient external compression of the upper arm prior to cardiac surgery was effective for reducing the occurrence of AKI (37.5% compared to 52.5% with sham; absolute risk reduction (ARR),15%; 95% CI, 2.56% to 27.44%; P=0.02). Fewer patients treated with RIPC received renal replacement therapy (RRT) (5.8% versus 15.8%; ARR, 10%; 95% CI, 2.25% to 17.75%; P=0.01). Moreover, the investigators found that the effectiveness of this intervention was strongly associated with the release of cell-cycle arrest biomarkers into the urine. Patients with urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]•[IGFBP7]) ≥ 0.5 (ng/ml)(ng/ml)/1000 before surgery had a significantly reduced rate of AKI compared to patients with lower urinary [TIMP-2]•[IGFBP7] concentration (relative risk (RR), 67%; 95% CI, 53% to 83%, P<0.001) whereas the biomarker concentrations after surgery predicted AKI as previously shown. This effect makes sense because cell-cycle arrest is thought to be part of the protective mechanisms endothelial cells use when exposed to stress. Stimulating these responses with RIPC should reduce AKI. Importantly, only 56% of patients treated with RIPC achieved an increase in urine [TIMP-2]•[IGFBP7] to ≥ 0.5, and only in this group was the intervention effective—patients that did not achieve this level showed no benefit.

Our goal is to eventually design and conduct a Bayesian 2-stage adaptive design sequence trial to evaluate the effectiveness of RIPC to prevent AKI in patients undergoing cardiac surgery. The dimensions of dose include duration, intensity and number of cycles. However, before this trial can be designed we need to answer 4 questions: i. Do baseline urinary [TIMP-2]•[IGFBP7] levels predict AKI (enrichment)? ii. Do [TIMP-2]•[IGFBP7] changes elicited by RIPC predict protection (RIPC efficacy measure)? iii. Is there a dose-response relationship between RIPC "dose" and [TIMP-2]•[IGFBP7]? iv. Is a dose-escalation RIPC protocol where doses are increased for non-responders, feasible and safe within the anesthesia workflow for cardiac surgery cases (practical)?


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Remote Ischemic Preconditioning to Prevent Acute Kidney Injury in High Risk Patients After Cardiac Surgery (RIPCRenal)
Study Start Date : December 2016
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Surgery

Arm Intervention/treatment
No Intervention: Observational group
No intervention, standard care
Sham Comparator: Sham RIPC
Three cycles of 5- min upper limb sham ischemia
Procedure: Remote ischemic preconditioning (RIPC)
3 cycles or more cycles of 5 to 10-min inflation of a blood-pressure cuff to 200 mm HG (or at least to a pressure 50 mmHG higher than the systolic arterial pressure) to one upper arm followed by 5 min reperfusion with the cuff deflated. In Non-Responder two additional cycles of 10 min cuff inflation will be performed in arm 6.

Experimental: RIPC-Group 1
Three cycles of 5- min upper limb ischemia
Procedure: Remote ischemic preconditioning (RIPC)
3 cycles or more cycles of 5 to 10-min inflation of a blood-pressure cuff to 200 mm HG (or at least to a pressure 50 mmHG higher than the systolic arterial pressure) to one upper arm followed by 5 min reperfusion with the cuff deflated. In Non-Responder two additional cycles of 10 min cuff inflation will be performed in arm 6.

Experimental: RIPC-Group 2
Three cycles of 7-min upper limb ischemia
Procedure: Remote ischemic preconditioning (RIPC)
3 cycles or more cycles of 5 to 10-min inflation of a blood-pressure cuff to 200 mm HG (or at least to a pressure 50 mmHG higher than the systolic arterial pressure) to one upper arm followed by 5 min reperfusion with the cuff deflated. In Non-Responder two additional cycles of 10 min cuff inflation will be performed in arm 6.

Experimental: RIPC-Group 3
Three cycles of 10-min upper limb ischemia
Procedure: Remote ischemic preconditioning (RIPC)
3 cycles or more cycles of 5 to 10-min inflation of a blood-pressure cuff to 200 mm HG (or at least to a pressure 50 mmHG higher than the systolic arterial pressure) to one upper arm followed by 5 min reperfusion with the cuff deflated. In Non-Responder two additional cycles of 10 min cuff inflation will be performed in arm 6.

Experimental: RIPC-Group 4
Three Cycles of 5-min upper limb ischemia. If there is no response this will be followed by 2 cycles of 10-min upper-limb ischemia
Procedure: Remote ischemic preconditioning (RIPC)
3 cycles or more cycles of 5 to 10-min inflation of a blood-pressure cuff to 200 mm HG (or at least to a pressure 50 mmHG higher than the systolic arterial pressure) to one upper arm followed by 5 min reperfusion with the cuff deflated. In Non-Responder two additional cycles of 10 min cuff inflation will be performed in arm 6.




Primary Outcome Measures :
  1. Change in urinary [TIMP-2]*[IGFBP7] [ Time Frame: within 12 hours after CPB ]
    Biomarkers will be measured at different time points after to evaluate the effect of RIPC on [TIMP-2]*[IGFBP7]


Secondary Outcome Measures :
  1. AKI within 72 hours [ Time Frame: 72 h ]
  2. Dialysis within 7 days of surgery [ Time Frame: 7 days ]
  3. All-cause-mortality at 90 days [ Time Frame: 90 d ]
  4. Dialysis at day 90 [ Time Frame: 90 days ]
  5. Renal recovery at day 90 [ Time Frame: 90 days ]
  6. MAKE 90 [ Time Frame: 90 days ]
    major adverse kidney events



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients who are scheduled to undergo cardiac surgery with cardiopulmonary bypass
  • Cleveland Clinic Score >=6

Exclusion Criteria:

  • Acute myocardial infarction up to 7 days before surgery
  • Age < 18 years
  • Off-pump cardiac surgery
  • Preexisting AKI
  • Chronic kidney disease (GFR < 30 ml/min)
  • Kidney transplantation within the last 12 months
  • Peripheral arterial occlusive disease
  • Pregnancy
  • Hepatorenal syndrome
  • Sulfonamide or thiazide medication within the last 7 days
  • Participation in another interventional trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02997748


Contacts
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Contact: Melanie Meersch, MD +49-251-8347282 aki@anit.uni-muenster.de

Locations
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Germany
University Hospital Muenster Recruiting
Muenster, Germany, D-48149
Contact: Alexander Zarbock, PhD, MD         
Sponsors and Collaborators
University Hospital Muenster
Else Kröner Fresenius Foundation
Investigators
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Study Chair: Melanie Meersch University Hospital Muenster

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Responsible Party: University Hospital Muenster
ClinicalTrials.gov Identifier: NCT02997748     History of Changes
Other Study ID Numbers: 04-AnIt-16
First Posted: December 20, 2016    Key Record Dates
Last Update Posted: January 30, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University Hospital Muenster:
acute kidney injury
cardiac surgery
Remote ischemic preconditioning
[TIMP-2]*[IGFBP7]

Additional relevant MeSH terms:
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Acute Kidney Injury
Renal Insufficiency
Kidney Diseases
Urologic Diseases