Trial Outcomes & Findings for RenalGuard System and Contrast Media (NCT NCT01098032)

Results Overview

The primary outcome measure will be the rate of development of CI-AKI in the 2 study arms (number of participants). CI-AKI is defined as an increase in the serum creatinine concentration \>=0.3 mg/dL from the baseline value at 48 hours after administration of the contrast media or the need for dialysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

294 participants

Primary outcome timeframe

at 48 hours following contrast exposure

Results posted on

2022-03-22

Participant Flow

All patients with CKD scheduled for coronary and/or peripheral angiography/angioplasty from January 2009 to December 2011 were screened for inclusion/exclusion criteria. The trial was conducted in across 4 interventional cardiology centers in Italy, according to the principles of the Declaration of Helsinki and Good Clinical Practice

Two enrolled patients did not finally undergo the scheduled treatment due to the occurrence fever or gastrointestinal bleeding

Participant milestones

Participant milestones
Measure	Systemic Alone Therapy Group Systemic alone therapy grou will be treated by intravenous sodium bicarbonate plus NAC administration. Patients allocated to the Systemic alone therapy group will receive 154 mEq/l of sodium bicarbonate in dextrose and H2O, according to the protocol reported by Merten et al. (9) The initial intravenous bolus was 3 ml/kg per hour for 1 hour immediately before contrast injection. Following this, patients will receive the same fluid at a rate of 1 ml/kg per hour during contrast exposure and for 6 hours after the procedure. All patients will receive NAC (Fluimucil, Zambon Group SpA, Milan, Italy) orally at a dose of 1200 mg twice daily on the day before and on the day of administration of the contrast agent (total of 2 days. Additional NAC dose (1.2 g) will be administered i.v. during the procedure.	RenalGuard System Group Prophylactic controlled hydration with saline (0.9%) plus N-acetylcystein (NAC; 6 g in total). In the RenalGuard group, an initial bolus (priming) of 250 ml will be administered. In case of left ventricular dysfunction (ejection fraction ≤30%) and/or unstable hemodynamic conditions the bolus will be reduced to 150 ml. Following the initial bolus, furosemide (0.25 mg/kg) will be administered in order to achieve the optimal urine flow (≥300 ml/h). The hydration will be continued throughout the duration of the procedure and will last 4 hours following the procedure. Additional doses of furosemide are allowed in case of decrease of urine flow \<300 ml/h.
Overall Study STARTED	147	147
Overall Study COMPLETED	146	146
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Systemic Alone Therapy Group Systemic alone therapy grou will be treated by intravenous sodium bicarbonate plus NAC administration. Patients allocated to the Systemic alone therapy group will receive 154 mEq/l of sodium bicarbonate in dextrose and H2O, according to the protocol reported by Merten et al. (9) The initial intravenous bolus was 3 ml/kg per hour for 1 hour immediately before contrast injection. Following this, patients will receive the same fluid at a rate of 1 ml/kg per hour during contrast exposure and for 6 hours after the procedure. All patients will receive NAC (Fluimucil, Zambon Group SpA, Milan, Italy) orally at a dose of 1200 mg twice daily on the day before and on the day of administration of the contrast agent (total of 2 days. Additional NAC dose (1.2 g) will be administered i.v. during the procedure.	RenalGuard System Group Prophylactic controlled hydration with saline (0.9%) plus N-acetylcystein (NAC; 6 g in total). In the RenalGuard group, an initial bolus (priming) of 250 ml will be administered. In case of left ventricular dysfunction (ejection fraction ≤30%) and/or unstable hemodynamic conditions the bolus will be reduced to 150 ml. Following the initial bolus, furosemide (0.25 mg/kg) will be administered in order to achieve the optimal urine flow (≥300 ml/h). The hydration will be continued throughout the duration of the procedure and will last 4 hours following the procedure. Additional doses of furosemide are allowed in case of decrease of urine flow \<300 ml/h.
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

RenalGuard System and Contrast Media

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Systemic Alone Therapy Group n=147 Participants Systemic alone therapy grou will be treated by intravenous sodium bicarbonate plus NAC administration. Patients allocated to the Systemic alone therapy group will receive 154 mEq/l of sodium bicarbonate in dextrose and H2O, according to the protocol reported by Merten et al. (9) The initial intravenous bolus was 3 ml/kg per hour for 1 hour immediately before contrast injection. Following this, patients will receive the same fluid at a rate of 1 ml/kg per hour during contrast exposure and for 6 hours after the procedure. All patients will receive NAC (Fluimucil, Zambon Group SpA, Milan, Italy) orally at a dose of 1200 mg twice daily on the day before and on the day of administration of the contrast agent (total of 2 days. Additional NAC dose (1.2 g) will be administered i.v. during the procedure.	RenalGuard System Group n=147 Participants Prophylactic controlled hydration with saline (0.9%) plus N-acetylcystein (NAC; 6 g in total). In the RenalGuard group, an initial bolus (priming) of 250 ml will be administered. In case of left ventricular dysfunction (ejection fraction ≤30%) and/or unstable hemodynamic conditions the bolus will be reduced to 150 ml. Following the initial bolus, furosemide (0.25 mg/kg) will be administered in order to achieve the optimal urine flow (≥300 ml/h). The hydration will be continued throughout the duration of the procedure and will last 4 hours following the procedure. Additional doses of furosemide are allowed in case of decrease of urine flow \<300 ml/h.	Total n=294 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants	14 Participants n=7 Participants	33 Participants n=5 Participants
Age, Categorical >=65 years	128 Participants n=5 Participants	133 Participants n=7 Participants	261 Participants n=5 Participants
Age, Continuous	75 years STANDARD_DEVIATION 9 • n=5 Participants	76 years STANDARD_DEVIATION 8 • n=7 Participants	75 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	57 Participants n=7 Participants	100 Participants n=5 Participants
Sex: Female, Male Male	104 Participants n=5 Participants	90 Participants n=7 Participants	194 Participants n=5 Participants
Region of Enrollment Italy	147 participants n=5 Participants	147 participants n=7 Participants	294 participants n=5 Participants

PRIMARY outcome

Timeframe: at 48 hours following contrast exposure

Population: all consecutive patients with chronic kidney disease scheduled for coronary and/or peripheral angiography and/or angioplasty with an estimated glomerular filtration rate (eGFR) ≤30 ml/min/1.73 m2 and/or a risk score ≥11 were considered eligible for the study

The primary outcome measure will be the rate of development of CI-AKI in the 2 study arms (number of participants). CI-AKI is defined as an increase in the serum creatinine concentration \>=0.3 mg/dL from the baseline value at 48 hours after administration of the contrast media or the need for dialysis.

Outcome measures

Outcome measures
Measure	Systemic Alone Therapy Group n=147 Participants Systemic alone therapy grou will be treated by intravenous sodium bicarbonate plus NAC administration. Patients allocated to the Systemic alone therapy group will receive 154 mEq/l of sodium bicarbonate in dextrose and H2O, according to the protocol reported by Merten et al. (9) The initial intravenous bolus was 3 ml/kg per hour for 1 hour immediately before contrast injection. Following this, patients will receive the same fluid at a rate of 1 ml/kg per hour during contrast exposure and for 6 hours after the procedure. All patients will receive NAC (Fluimucil, Zambon Group SpA, Milan, Italy) orally at a dose of 1200 mg twice daily on the day before and on the day of administration of the contrast agent (total of 2 days. Additional NAC dose (1.2 g) will be administered i.v. during the procedure.	RenalGuard System Group n=147 Participants Prophylactic controlled hydration with saline (0.9%) plus N-acetylcystein (NAC; 6 g in total). In the RenalGuard group, an initial bolus (priming) of 250 ml will be administered. In case of left ventricular dysfunction (ejection fraction ≤30%) and/or unstable hemodynamic conditions the bolus will be reduced to 150 ml. Following the initial bolus, furosemide (0.25 mg/kg) will be administered in order to achieve the optimal urine flow (≥300 ml/h). The hydration will be continued throughout the duration of the procedure and will last 4 hours following the procedure. Additional doses of furosemide are allowed in case of decrease of urine flow \<300 ml/h.
Number of Participants With Contrast-induced Acute Kidney Injury	146 participants	146 participants

SECONDARY outcome

Timeframe: 7 days

an increase in the serum creatinine concentration \>=0.25% and \>=0.5 mg/dl at 48 hours after contrast exposure

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 7 days

Cystatin C is an alternative biomarker of kidney damage. Cystatin C seems to be superior to serum creatinine an identifying kidney function and damage.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 7 days

NGAL is a new biomarker which seems to be very promising in detecting kidney injury. prelimiary data suggest that urine and serum NGAL increase very early (within few horurs) after the occurrence og acute kidney damage. Therefore, NGAL may be a real marker of acute kidney injury.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 month

occurrence of renal failure requiring dialysis represents the haard endpoint of the study. Actually this represents the worst clinical consequence of CI-AKI.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 month

Assessment of the rate of in-hospital major adverse events (i.e. acute myocardial infarction, c) renal failure requiring dialysis, and d) acute pulmonary edema) will give important informantion on the clinical relevance of prophylactic strategies in preventing CI-AKI

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 month

Assessement of the cost-effectiveness ratio is important when testing a new strategy of both therapy and prophylaxis. The Renalguard system is more expensive than the conventional hydration regimen. The cost of RenalGuard system is approximately 800 $. This cost will be justified only if the system is more effective in preventing CI-AKI and improving the clinical outcome, expecially reducing the lenght of ospedalization and the rate of dialysis.

Outcome measures

Outcome data not reported

Adverse Events

RenalGuard System Group

Serious events: 10 serious events

Other events: 10 other events

Deaths: 0 deaths

Systemic Alone Therapy Group

Serious events: 14 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	RenalGuard System Group n=146 participants at risk Prophylactic controlled hydration with saline (0.9%) plus N-acetylcystein (NAC; 6 g in total). In the RenalGuard group, an initial bolus (priming) of 250 ml will be administered. In case of left ventricular dysfunction (ejection fraction ≤30%) and/or unstable hemodynamic conditions the bolus will be reduced to 150 ml. Following the initial bolus, furosemide (0.25 mg/kg) will be administered in order to achieve the optimal urine flow (≥300 ml/h). The hydration will be continued throughout the duration of the procedure and will last 4 hours following the procedure.	Systemic Alone Therapy Group n=146 participants at risk Systemic alone therapy group was treated by intravenous sodium bicarbonate plus NAC administration.
General disorders Death	4.1% 6/146 • Number of events 6 • 1 month	4.1% 6/146 • Number of events 6 • 1 month
Renal and urinary disorders Dialysis	0.68% 1/146 • Number of events 1 • 1 month	4.8% 7/146 • Number of events 7 • 1 month
Cardiac disorders Acute pulmonary edema	2.1% 3/146 • Number of events 3 • 1 month	0.68% 1/146 • Number of events 1 • 1 month

Other adverse events

Other adverse events
Measure	RenalGuard System Group n=146 participants at risk Prophylactic controlled hydration with saline (0.9%) plus N-acetylcystein (NAC; 6 g in total). In the RenalGuard group, an initial bolus (priming) of 250 ml will be administered. In case of left ventricular dysfunction (ejection fraction ≤30%) and/or unstable hemodynamic conditions the bolus will be reduced to 150 ml. Following the initial bolus, furosemide (0.25 mg/kg) will be administered in order to achieve the optimal urine flow (≥300 ml/h). The hydration will be continued throughout the duration of the procedure and will last 4 hours following the procedure.	Systemic Alone Therapy Group n=146 participants at risk Systemic alone therapy group was treated by intravenous sodium bicarbonate plus NAC administration.
Renal and urinary disorders Micturation	2.7% 4/146 • Number of events 4 • 1 month	0.00% 0/146 • 1 month
Metabolism and nutrition disorders Hypokalemia	4.1% 6/146 • Number of events 6 • 1 month	2.1% 3/146 • Number of events 3 • 1 month

Additional Information

Dr. Carlo Briguori, Principal Investigator

Clinica Mediterranea

Phone: +390817259

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place