Personalized Mean Arterial Pressure Management on Renal Function During Septic Shock (DORESEP)

Personalized Haemodynamic Management of Septic Shock: Influence of Mean Arterial Pressure Level on Renal Function: Randomized Controlled Trial

Sepsis is the most severe complication of infections. Sepsis-associated Acute kidney injury (AKI) is commonly encountered in critically ill patients and independently predicts poor outcome. Unfortunately, no drug or management strategy was able to reduce incidence of AKI. To adapt the level of mean arterial pressure according to local renal hemodynamic evaluated by renal Doppler could lead to a better renal perfusion, and then less AKI.

Study Overview

• Status: Completed
• Conditions: Septic Shock; Acute Kidney Injury
• Intervention / Treatment: Other: Haemodynamic management; Other: Haemodynamic management

Detailed Description

Acute Kidney Injury (AKI) is a frequent and serious complication of sepsis. Renal ischemia plays a major role in the pathophysiology of sepsis-associated AKI. There is currently no treatment to prevent or to treat AKI. It has been shown that a resistivity index (RI) greater than 0.74 of patients with septic shock could predict the occurrence of renal failure, and that increase mean arterial pressure (MAP) with norepinephrine could decrease RI. Hence, we propose to compare the frequency and the severity of the sepsis-associated AKI according to the early hemodynamic management of septic shock. Patients will be randomized in a classic group (MAP 65 mmHg) and an interventional group (MAP 85 mmHg). We can thus determine whether the level of MAP influences renal function, and whether this influence of MAP is dependent of renal perfusion assessed by renal Doppler.

Participants will be followed for the duration of hospital stay, an expected average of 4 weeks.

Primary endpoint:

-Presence and severity of sepsis-associated AKI at day 7.

Secondary endpoints:

• Acute renal failure measured by Classification AKI at day 28.
• Acute renal failure as measured by the RIFLE classification in the fourth to seventh day and 28th day.
• Use of renal replacement therapy during hospitalization in intensive care unit
• Mortality at day 28 Duration of study: Recruitment: 10 months, the patient monitoring: 28 days ± 3 days, total test duration: 11 months

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Kremlin Bicêtre, France, 94275
    • Reanimation Chirurgicale - Hôpital Kremlin Bicêtre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Any patient with septic shock may be included in the next 6 to 16h
• Age > 18 years old and <= 80 years

Exclusion Criteria:

• Chronic renal failure (Baseline serum creatinine > 120 mmol/L)
• Chronic cardiac failure (Left ventricle ejection fraction < 40%)
• Pregnancy
• Urinary Tract Infection
• Patients with a left ventricular dysfunction ( ventricular ejection fraction <40%)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test group; Patients will be treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they will be randomized in two groups. In the first group (study group, n=30), mean arterial pressure will be increased to 85 mm Hg for 72 hours by increasing the dose of norepinephrine in patients (A maximum dose of 1.2 mcg / kg / min is not exceeded). Key details, e.g., for drugs include dosage form, dosage, frequency and duration.	Other: Haemodynamic management; Patients will be treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they will be randomized in two groups. In the first group (study group, n=30), mean arterial pressure will be increased to 85 mm Hg for 72 hours by increasing the dose of norepinephrine in patients.; Other: Haemodynamic management; Patients will be treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they will be randomized in two groups. In this group (control group, n=30), mean arterial pressure will be maintained at 65 mm Hg.
Active Comparator: Control group; Patients will be treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they will be randomized in two groups. In this group (control group, n=30), mean arterial pressure will be maintained at 65 mm Hg.	Other: Haemodynamic management; Patients will be treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they will be randomized in two groups. In the first group (study group, n=30), mean arterial pressure will be increased to 85 mm Hg for 72 hours by increasing the dose of norepinephrine in patients.; Other: Haemodynamic management; Patients will be treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they will be randomized in two groups. In this group (control group, n=30), mean arterial pressure will be maintained at 65 mm Hg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Acute kidney injury according to RIFLE score	at 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for renal replacement therapy	including metabolic indications (Azotemia Serum urea ≥ 36mmol/L (100 mg/dL) ; Uremic complications : encephalopathy, pericarditis, bleeding ; Hyperkalemia K+ ≥ 6 mmol/L and/or electrocardiogram abnormalities ; Hypermagnesemia ≥4 mmol/L and/or anuria/absent deep tendon reflexes ; Acidosis Serum pH ≤ 7.15), Oligo-anuria Urine output <200mL/12 h or anuria, Fluid overload like Diuretic-resistant organ edema in the presence of acute kidney injury.	during hospitalization
All cause mortality	All Cause mortality at 28 days, including refractory shock, refractory hypoxia, multiple organ failure, decisions to forgo life-sustaining therapies (DFLSTs)	at 28 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: October 14, 2011
• First Submitted That Met QC Criteria: November 14, 2011
• First Posted (Estimate): November 17, 2011

Study Record Updates

• Last Update Posted (Actual): January 10, 2020
• Last Update Submitted That Met QC Criteria: January 8, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Sepsis; Acute kidney injury; Catecholamines; Mean arterial pressure; Renal doppler
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Kidney Diseases; Urologic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Renal Insufficiency; Sepsis; Shock, Septic; Shock; Acute Kidney Injury
• Other Study ID Numbers: P091103