Remote Ischemic Preconditioning After Cardiac Surgery (RIPCRenal)
Remote Ischemic Preconditioning to Prevent Acute Kidney Injury in High Risk Patients After Cardiac Surgery (RIPCRenal)
Przegląd badań
Status
Interwencja / Leczenie
Szczegółowy opis
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)?
Typ studiów
Zapisy (Oczekiwany)
Faza
- Nie dotyczy
Kontakty i lokalizacje
Lokalizacje studiów
-
-
-
Muenster, Niemcy, D-48149
- Rekrutacyjny
- University hospital Muenster
-
Kontakt:
- Alexander Zarbock, PhD, MD
-
-
Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Opis
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
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Randomizowane
- Model interwencyjny: Przydział równoległy
- Maskowanie: Potroić
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
|---|---|
|
Brak interwencji: Observational group
No intervention, standard care
|
|
|
Pozorny komparator: Sham RIPC
Three cycles of 5- min upper limb sham ischemia
|
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.
|
|
Eksperymentalny: RIPC-Group 1
Three cycles of 5- min upper limb ischemia
|
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.
|
|
Eksperymentalny: RIPC-Group 2
Three cycles of 7-min upper limb ischemia
|
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.
|
|
Eksperymentalny: RIPC-Group 3
Three cycles of 10-min upper limb ischemia
|
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.
|
|
Eksperymentalny: 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
|
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.
|
Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Change in urinary [TIMP-2]*[IGFBP7]
Ramy czasowe: within 12 hours after CPB
|
Biomarkers will be measured at different time points after to evaluate the effect of RIPC on [TIMP-2]*[IGFBP7]
|
within 12 hours after CPB
|
Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
AKI within 72 hours
Ramy czasowe: 72 h
|
72 h
|
|
|
Dialysis within 7 days of surgery
Ramy czasowe: 7 days
|
7 days
|
|
|
All-cause-mortality at 90 days
Ramy czasowe: 90 d
|
90 d
|
|
|
Dialysis at day 90
Ramy czasowe: 90 days
|
90 days
|
|
|
Renal recovery at day 90
Ramy czasowe: 90 days
|
90 days
|
|
|
MAKE 90
Ramy czasowe: 90 days
|
major adverse kidney events
|
90 days
|
Współpracownicy i badacze
Sponsor
Współpracownicy
Śledczy
- Krzesło do nauki: Melanie Meersch, University hospital Muenster
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów
Zakończenie podstawowe (Oczekiwany)
Ukończenie studiów (Oczekiwany)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Oszacować)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Dodatkowe istotne warunki MeSH
Inne numery identyfikacyjne badania
- 04-AnIt-16
Plan dla danych uczestnika indywidualnego (IPD)
Planujesz udostępniać dane poszczególnych uczestników (IPD)?
Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .