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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT02997748
Other study ID # 04-AnIt-16
Secondary ID
Status Recruiting
Phase N/A
First received December 15, 2016
Last updated January 29, 2018
Start date December 2016
Est. completion date September 2019

Study information

Verified date January 2018
Source University Hospital Muenster
Contact Melanie Meersch, MD
Phone +49-251-8347282
Email aki@anit.uni-muenster.de
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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)?


Recruitment information / eligibility

Status Recruiting
Enrollment 180
Est. completion date September 2019
Est. primary completion date June 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

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.

Locations

Country Name City State
Germany University Hospital Muenster Muenster

Sponsors (2)

Lead Sponsor Collaborator
University Hospital Muenster Else Kröner Fresenius Foundation

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change in urinary [TIMP-2]*[IGFBP7] Biomarkers will be measured at different time points after to evaluate the effect of RIPC on [TIMP-2]*[IGFBP7] within 12 hours after CPB
Secondary AKI within 72 hours 72 h
Secondary Dialysis within 7 days of surgery 7 days
Secondary All-cause-mortality at 90 days 90 d
Secondary Dialysis at day 90 90 days
Secondary Renal recovery at day 90 90 days
Secondary MAKE 90 major adverse kidney events 90 days