Remote Ischemic Preconditioning After Cardiac Surgery

NCT ID: NCT02997748

Last Updated: 2018-01-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2019-09-30

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.

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)?

Conditions

Cardiac Surgery, Aortocoronary Bypass

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Observational group

No intervention, standard care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Sham RIPC

Three cycles of 5- min upper limb sham ischemia

Group Type: SHAM_COMPARATOR

Remote ischemic preconditioning (RIPC)

Intervention Type: PROCEDURE

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.

RIPC-Group 1

Three cycles of 5- min upper limb ischemia

Group Type: EXPERIMENTAL

Remote ischemic preconditioning (RIPC)

Intervention Type: PROCEDURE

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.

RIPC-Group 2

Three cycles of 7-min upper limb ischemia

Group Type: EXPERIMENTAL

Remote ischemic preconditioning (RIPC)

Intervention Type: PROCEDURE

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.

RIPC-Group 3

Three cycles of 10-min upper limb ischemia

Group Type: EXPERIMENTAL

Remote ischemic preconditioning (RIPC)

Intervention Type: PROCEDURE

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.

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

Group Type: EXPERIMENTAL

Remote ischemic preconditioning (RIPC)

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: PROCEDURE

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Else Kröner Fresenius Foundation

OTHER

Sponsor Role: collaborator

University Hospital Muenster

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Melanie Meersch

Role: STUDY_CHAIR

University Hospital Muenster

Locations

University Hospital Muenster

Münster, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Melanie Meersch, MD

Role: CONTACT

aki@anit.uni-muenster.de

+49-251-8347282

Facility Contacts

Alexander Zarbock, PhD, MD

Role: primary

Other Identifiers

04-AnIt-16

Identifier Type: -

Identifier Source: org_study_id