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

Acute Kidney Injury Clinical Trial

— UNICORN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03715868
• Other study ID #: 004
• Status: Completed
• Phase: N/A
• Start date: January 15, 2019
• Est. completion date: August 24, 2020

Study information

• Verified date: April 2021
• Source: University of Cologne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 117
• Est. completion date: August 24, 2020
• Est. primary completion date: August 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Acute Renal Failure
• Renal Insufficiency
• Wounds and Injuries

Intervention

Other:
• Non-milked derived protein source formula diet
Formula diet based on a non-milked derived protein source

Locations

Country	Name	City	State
Germany	University Hospital of Cologne	Cologne

Sponsors (2)

Lead Sponsor	Collaborator
University of Cologne	Fresenius Kabi

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AKI incidence within 72 hours according KDIGO classification after induction of ischemia ('cross clamping') in comparison to baseline values	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.	Pre-operative baseline day of surgery to 72 hours after induction of ischemia
Secondary	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
Secondary	Incidence of AKI as defined by KDIGO until discharge		Pre-operative baseline day of surgery to day of discharge, an expected average of 10 days
Secondary	Occurrence of AKI according to KDIGO I, II, III		Pre-operative baseline day of surgery to day of discharge, an expected average of 10 days
Secondary	Maximum serum creatinine concentration detected postoperatively during hospitalization		Pre-operative baseline day of surgery to day of discharge, an expected average of 10 days
Secondary	Need for renal replacement treatment during hospitalization		Patient will be followed up for the duration of hospital stay, an expected average of 10 days
Secondary	In-hospital mortality		Patient will be followed up for the duration of hospital stay, an expected average of 10 days
Secondary	Length of hospital stay		Patient will be followed up for the duration of hospital stay, an expected average of 10 days
Secondary	Length of stay on intensive care unit (ICU)		Day of admittance until day of discharge from ICU, an expected average of 2 days
Secondary	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
Secondary	C-reactive Protein (CRP) concentration		Pre-operative day of surgery and at 24 hours after onset of ischemia
Secondary	Leukocyte count		Pre-operative day of surgery and at 24 hours after onset of ischemia
Secondary	Creatine kinase concentration		Pre-operative day of surgery and at 24 hours after onset of ischemia
Secondary	Troponin T concentration		Pre-operative day of surgery and at 24 hours after onset of ischemia
Secondary	Lactate Dehydrogenase concentration		Pre-operative day of surgery and at 24 hours after onset of ischemia
Secondary	N-terminal Pro brain natriuretic peptide (NT-ProBNP) concentration		Pre-operative day of surgery and at 24 hours after onset of ischemia
Secondary	Lactate concentration		Pre-operative day of surgery and at 24 hours after onset of ischemia
Secondary	Amino acid pattern (concentrations), Insulin concentration, insulin-like growth factors (IGF1) concentration, glucose concentration		Before start of diet and on day of admission (before surgery)
Secondary	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
Secondary	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