Evaluation of the Efficacy and Safety of Regional Anticoagulation With Citrate in Extended Hemodialysis in Patients With Acute Renal Injury Admitted to an Intensive Care Unit
Trial Snapshot
- Phase
- Phase 3
- Status
- Suspended
- Enrollment
- 200
- Locations
- 1
- Primary Endpoint
- Clotting rate
Study Overview
Brief Summary
Data on regional citrate anticoagulation in patients with acute kidney injury (AKI) treated by hybrid or extended dialysis are scarce and heterogeneous. The path batch system (Genius®) or the proportion hemodialysis machines are well suited equipments to perform extended dialysis. However, clotting of the system might occur with relatively high frequency, especially in critically ill patients with high risk of clotting or in those with contraindication to the use of heparin.
The aims of this study are: 1) to test and to validate a new protocol using citrate to perform regional anticoagulation in AKI patients admitted to the intensive care unit (ICU) and treated by extended dialysis, using a control group (use of heparin or intermittent saline flush) as comparison in the Heart Institute of the university medical complex "Clinics Hospital Medical School at São Paulo" (Hospital das Clínicas da Faculdade de Medicina do Estado de São Paulo) and at the Cancer Institute of the São Paulo State; 2) to evaluate the anticoagulation in these procedures with citrate and compare with the control group using heparin or saline flush, so the primary end point would be the rates of system clotting; 3) to study the calcium mass transfer in these procedures and its impact on bone metabolism in these patients. The inclusion criteria are all AKI patients admitted in these places and candidates to renal replacement therapy using the extended dialysis, age above 18 years. The exclusion criteria are acute liver failure, hemorrhagic stroke, platelets level below 20,000/mm3, and active bleeding needing transfusional support (two or more red cell packs in 24 hours).
Detailed Description
The investigators conduct an open label randomized clinical trial with cross-over between the groups. The study will be performed in all the intensive care units (ICU) at the Heart Institute and the Cancer Institute, both hospitals related with the University of São Paulo Medical School, at the city of São Paulo, Brazil.
All inpatients over 18 years in the ICU with acute kidney injury (AKI) who are arranged for extended hemodialysis will be invited to participate in the study. After signing an informed consent formulary, the patients went to randomization between two groups: citrate or control therapy. The research team randomly drawn the patients using a box with twenty entries for each group, totalizing forty units. Thus, after the inclusion of forty patients, it is guaranteed that half of them will start in the citrate group and the other half in the control group. Afterwards, the box is refilled to its maximum capacity of forty units for the next draw.
The randomization process determine the type of anticoagulation that the patient will be submitted in the first dialysis session. Subsequently the subject will participate in the other group, alternating between the two modalities until the maximum of six extended dialysis for the protocol.
In the control group, the decision on the use of heparin or continuous saline infusion as an anticoagulation method will be based on the presence of contraindications to the heparin use, which would be I) platelet levels <150,000/mm3; II) active or recent bleeding; III) reduction in hemoglobin levels of more than 2.0g/dl in less than 24 hours; IV) invasive procedures or surgeries realized in the last 7 days or scheduled to the next 24 hours.
There may be a change in the choice of method (citrate versus control), if the nephrologist consultant team deems it necessary, due to demands of care, particularly if there is early or repeated coagulation of the system. The proper functioning of the hemodialysis catheter will be evaluated before the dialysis initiation, and in case of malfunction, it will be properly replaced before the procedure starts.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •All patients with acute kidney injury admitted to the intensive care unit and candidates for extended dialysis (renal replacement therapy)
- •Age over 18 years.
Exclusion Criteria
- •Acute liver failure
- •Hemorrhagic stroke in the last 30 days
- •Patients with platelet levels below 20,000/mm3
- •Active bleeding requiring transfusion (two or more red blood cell packs within 24 hours)
Arms & Interventions
Control Group
Patients in this group will receive heparin during hemodialysis sessions, at a dose of 1.000 units at the beginning and 500 units per hour in a syringe infusion pump.
If the patient has a contraindication for the heparin use, it will receive saline continuous administration.
This is the actual standard of care performed in extended hemodialysis sessions.
Intervention: Control Group (heparin or continuous saline) (Drug)
Citrate Group
Patients in this group will receive regional citrate anticoagulation, with acid-citrate-dextrose 2.2% (ACD). Dose of 3 mmol per liter of filtered blood. The systemic calcium levels are measured every two hours and a solution of calcium chloride is infused in a peripheral venous access, accordingly to citrate infusion rate and the systemic calcium values.
Intervention: Citrate Anticoagulation Solution (Drug)
Outcomes
Primary Outcomes
Clotting rate
Time Frame: through all dialysis session, an average of 8 hours
Clotting of the dialysis system with complete impossibility to continue the therapy
Secondary Outcomes
- Serum phosphorus(through all dialysis session, an average of 8 hours)
- Serum magnesium(through all dialysis session, an average of 8 hours)
- Serum bicarbonate(through all dialysis session, an average of 8 hours)
- Parathyroid hormone (PTH), Fibroblast growth factor-23 (FGF-23), Procollagen type 1 N-terminal propeptide (P1NP), Esclerostin and Telopeptide carboxiterminal of type I collagen (cTX)(through all dialysis session, an average of 8 hours)
- Dialysate calcium(through all dialysis session, an average of 8 hours)
- Parathyroid hormone (PTH) concentration(two measurements per patient (before the dialysis initiation and at the end, after an average of 8 hours))
- Procollagen type 1 N-terminal propeptide (P1NP) concentration(baseline, before the dialysis initiation)
- Sclerostin concentration(baseline, before the dialysis initiation)
- Telopeptide carboxyterminal of type I collagen (cTX) concentration(baseline, before the dialysis initiation)
- Mean arterial pressure(every hour in the dialysis session (an average of 8 hours))
- Heart rate(every hour in the dialysis session (an average of 8 hours))
- Respiratory rate(every hour in the dialysis session (an average of 8 hours))
- Temperature(every hour in the dialysis session (an average of 8 hours))
- Serum ionized and total calcium levels(through all dialysis session, an average of 8 hours)
- Serum sodium concentration(through all dialysis session, an average of 8 hours)
- Serum potassium concentration(through all dialysis session, an average of 8 hours)
- Serum creatinine concentration(through all dialysis session, an average of 8 hours)
- Serum urea concentration(through all dialysis session, an average of 8 hours)
- Fibroblast growth factor-23 (FGF-23) concentration(baseline, before the dialysis initiation)
Investigators
EMMANUEL DE ALMEIDA BURDMANN
Principal Investigator
University of Sao Paulo General Hospital