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Pre-operative Short-term Administration of a Formula Diet Containing a Non-milk-derived Protein Source for Prevention of Acute Kidney Injury After Cardiac Surgery

Not Applicable
Completed
Conditions
Acute Renal Failure
Acute Kidney Injury
Interventions
Other: Non-milked derived protein source formula diet
Registration Number
NCT03715868
Lead Sponsor
University of Cologne
Brief Summary

Cardiac surgery is associated with a high risk of postoperative AKI with significant morbidity and mortality. To date, no preventive or therapeutic measures exist to prevent this. According to the data from animal trials, a preoperative diet with a deficiency of milk-derived proteins may be a new preventive measure in this context.

This trial will investigate whether one week of changing the diets protein source to a non-milk-derived one prior to surgery effectively induces renal protection from post-surgery AKI in humans. Patients undergoing elective cardiac surgery are randomized into two arms. In the non-milked-derived based diet arm, patients receive an appropriate formula diet based on a protein source other than milk derived proteins. In the control arm, patients are provided with a formula diet based on milk-protein. Total amount of calories and proteins is not restricted and - due to randomization - assumed not to be significantly different between the two arms.

Detailed Description

Cardiac surgery is associated with a high risk of postoperative AKI with significant morbidity and mortality. Acute kidney injury (AKI) constitutes a significant complication in hospitalized patients with an incidence of about 30%. Depending on existing comorbidities, a mortality of up to 60% occurs in critically ill or postoperative patients with AKI. To date, no preventive or therapeutic measures exist to prevent this. According to the data from animal trials, a preoperative diet low in sulfur-containing amino acids may be a new preventive measure in this context.

This trial will investigate whether one week of changing the diets protein source to a non-milk-derived one prior to surgery effectively induces renal protection from post-surgery AKI in humans. Patients undergoing elective cardiac surgery are randomized into two arms.

In the non-milked-derived based diet arm, patients receive an appropriate formula diet based on a protein source other than milk derived proteins. The formula diet replaces the regular diet completely from day -7 until the scheduled cardiothoracic surgery. The amount of formula diet is based on individual calculations to cover the patients daily energy demand.

In the control arm, patients are provided with a formula diet based on milk-protein, accordingly. Total amount of calories and proteins is not restricted and - due to randomization - assumed not to be significantly different between the two arms.

The primary endpoint of the clinical trial is to investigate whether a preoperative diet with a deficiency of milk-derived proteins leads to a reduction of AKI incidence within 72 hours after surgery. AKI is defined according to 'Kidney Disease: Improving Global Outcomes' (KDIGO) classification as an increase in serum creatinine of ≥0.3 mg/dl within 48 hours, or an increase of serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days, or a reduction of urine output to \<0.5ml/kg/hour for more than 6 hours.

Baseline creatinine will be assessed prior to the start of the surgical procedure. The time frame for the following assessments with respect to the primary endpoint will be 72 hours from the onset of ischemia (cross-clamping). Blood samples will be obtained at 24 hours, 48 hours, and 72 hours after cross-clamping. Hourly urine output will be assessed as long as a Foley-catheter is in place.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
117
Inclusion Criteria
  1. Men and women ≥50 years of age
  2. Caucasian ethnicity
  3. Scheduled cardiac surgery with use of the heart-lung machine with a lead time of at least 9 days
  4. Written informed consent
Exclusion Criteria
  1. Chronic renal replacement therapy
  2. Status post kidney transplantation
  3. Vegetarian lifestyle
  4. BMI <18.5 kg/m2
  5. Calorie-reduced diet within the preceding 4 weeks
  6. Underlying wasting disease
  7. Uncontrolled local or systemic infection
  8. Contraindication for enteral nutrition
  9. Known allergy to or intolerance of the ingredients of the formula diets used
  10. Pregnancy or breastfeeding
  11. Absence of safe contraceptive measures or non-occurrence of menopause (in women)
  12. Participation in other interventional trials
  13. Persons who are in a dependency/employment relationship with the investigators
  14. Accommodation in an institution by judicial or administrative order.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Non-milked derived protein source formula dietNon-milked derived protein source formula dietFormula diet based on a non-milked derived protein source
Primary Outcome Measures
NameTimeMethod
AKI incidence within 72 hours according KDIGO classification after induction of ischemia ('cross clamping') in comparison to baseline valuesPre-operative baseline day of surgery to 72 hours after induction of ischemia

The primary endpoint of the clinical trial is to investigate whether a preoperative diet with a non-milked derived protein source leads to a reduction of AKI incidence within 72 hours after surgery. AKI is defined according to KDIGO as an increase in serum creatinine of ≥0.3 mg/dl within 48 hours, or an increase of serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days, or a reduction of urine output to \<0.5ml/kg/hour for more than 6 hours.

Baseline creatinine will be assessed prior to the start of the surgical procedure. The time frame for the following assessments with respect to the primary endpoint will be 72 hours from the onset of ischemia (cross-clamping). Blood samples will be obtained at 24 hours, 48 hours, and 72 hours after cross-clamping. Hourly urine output will be assessed as long as a Foley-catheter is in place.

Secondary Outcome Measures
NameTimeMethod
Absolute and relative increase of serum creatinine concentration at 24 hours, 48 hours, and 72 hours after cardiac surgery ("cross clamping")Pre-operative baseline day of surgery and 24 hours, 48 hours and 72 hours after induction of ischemia
Incidence of AKI as defined by KDIGO until dischargePre-operative baseline day of surgery to day of discharge, an expected average of 10 days
In-hospital mortalityPatient will be followed up for the duration of hospital stay, an expected average of 10 days
Length of stay on intensive care unit (ICU)Day of admittance until day of discharge from ICU, an expected average of 2 days
tissue inhibitor of metalloproteinases 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) urine concentrations before surgery and at 4 hours and 24 hours after onset of ischemia (NephroCheck Test)Pre-operative baseline day of surgery and at 4 hours and 24 hours after induction of ischemia
C-reactive Protein (CRP) concentrationPre-operative day of surgery and at 24 hours after onset of ischemia
Leukocyte countPre-operative day of surgery and at 24 hours after onset of ischemia
Lactate Dehydrogenase concentrationPre-operative day of surgery and at 24 hours after onset of ischemia
Amino acid pattern (concentrations), Insulin concentration, insulin-like growth factors (IGF1) concentration, glucose concentrationBefore start of diet and on day of admission (before surgery)
Need for renal replacement treatment during hospitalizationPatient will be followed up for the duration of hospital stay, an expected average of 10 days
Length of hospital stayPatient will be followed up for the duration of hospital stay, an expected average of 10 days
Troponin T concentrationPre-operative day of surgery and at 24 hours after onset of ischemia
N-terminal Pro brain natriuretic peptide (NT-ProBNP) concentrationPre-operative day of surgery and at 24 hours after onset of ischemia
Occurrence of AKI according to KDIGO I, II, IIIPre-operative baseline day of surgery to day of discharge, an expected average of 10 days
Maximum serum creatinine concentration detected postoperatively during hospitalizationPre-operative baseline day of surgery to day of discharge, an expected average of 10 days
Creatine kinase concentrationPre-operative day of surgery and at 24 hours after onset of ischemia
Mortality rate at 30 and 180 days (as followed-up upon by telephone call)Day of surgery until 180 days after time point of surgery
Need for renal replacement therapy within 180 days after time point of surgery (as followed-up upon by telephone call)Day of surgery until 180 days after time point of surgery
Lactate concentrationPre-operative day of surgery and at 24 hours after onset of ischemia

Trial Locations

Locations (1)

University Hospital of Cologne

🇩🇪

Cologne, Germany

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