Clinical trial NCT06570187: The Effect of Dexmedetomidine on the Renal Functions in Septic Critically Ill Patients
Official title: The Effect of Dexmedetomidine on the Renal Functions in Septic Critically Ill Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Sepsis
Septic Shock
Acute Kidney Injury
Keywords: Dexmedetomidine
acute kidney injury
sepsis
critically ill patients
sedation
prospective clinical trial
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2024-08-26
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly distributed into two groups:

1. Group one: 64 adult participants receiving standard treatment of sepsis and septic shock with dexmedetomidine.
2. Group two: 64 adult participants receiving standard treatment of sepsis and septic shock and the standard sedatives without dexmedetomidine.

Both groups can receive other sedatives as add-ons if needed. Guided by Richmond Agitation and Sedation Scale (RASS) and clinical response.
Primary purpose: SUPPORTIVE_CARE

Brief summary: This clinical trial aims to evaluate the effect of dexmedetomidine in Sepsis-Associated Acute Kidney Injury in critically ill patients by answering the following questions:

1. What is dexmedetomidine's effect on kidney functions?
2. What is the safety and efficacy of dexmedetomidine in Sepsis-Associated Acute Kidney Injury?

The investigator will compare dexmedetomidine to the standard sedative.

The Participant will take either dexmedetomidine or the standard sedative during their hospitalization, with follow-up of the following:

1. Vital signs including blood pressure, body temperature, respiratory rate, heart rate, and oxygen saturation.
2. Laboratory data including kidney function tests, electrolytes, complete blood count, and liver function tests.
3. An electrocardiogram will be followed to check the heart's electrical activity.
4. The level of alertness or agitation to avoid over and under-sedation.
5. The level of organ dysfunction and mortality risks.
6. Duration of mechanical ventilation.
7. Duration of hospitalization.

Detailed description: Recently, it has been confirmed that dexmedetomidine has an organ protective effect, including the nervous system, heart, lungs, kidneys, liver, and small intestine. These properties allow dexmedetomidine to be a promising candidate for clinical multiorgan protection.

Aim of the study: Evaluation of the effect of dexmedetomidine in Sepsis-Associated Acute Kidney Injury (SA-AKI).

Objectives:

1. Assessment of dexmedetomidine effect in SA-AKI through following serum creatinine (SCr) level, urinary output (UOP), and the need for renal replacement therapy (RRT).
2. Assessment of dexmedetomidine safety in SA-AKI through following the incidence of new-onset bradycardia, and hypotension requiring intervention.
3. Assessment of dexmedetomidine efficacy by determining the effect on hospital mortality, duration of mechanical ventilation (MV), days free of agitation, incidence of organ dysfunction other than AKI, and length of hospital and ICU stay.

Study Design:

The study will be a prospective, randomized, parallel, controlled, open-label clinical trial including 128 participants with SA-AKI. Participants will be recruited from the Critical Care Department at Cairo University Hospitals. Randomization will be carried out using Random Allocation Software. Patients will be randomly allocated into two groups after screening for inclusion and exclusion criteria.

Written informed consent will be obtained from participants' legal caregivers.

Ethical committee approval will be available.

The primary investigator will be responsible for data collection. Each participant will be presented using a sequential number.

Participants recruitment and concealment allocation, data collection, data management, and data analysis will all be subjected to supervision and on-site auditing by academic and medical supervisors. For data verification, medical records revision will be done, to ensure the accuracy and completeness of the collected data.

Based on the pattern and percentage of missing data, the study investigator is expecting either missing completely at random (MCAR) or missing at random (MAR). Accordingly, multiple imputation (MI) will be implemented to handle missing data.

Normal ranges for lab data will be available.

Study outcomes will be assessed every 48 hours.

Sample size calculation:

Sample size calculation was performed using G power software. The sample size was based on an effect size of 0.5272. A total sample size of 116 patients (58 patients per group) is needed to reject the null hypothesis of equality of means between the control and treatment groups with an 80% power at a 5% significance level (α = 0.05) using two tails t-test.

The effect size was calculated based on the difference in SCr between day 1 and day 3 in septic AKI patients (126.3µmol/L ± 27.6 in day 1 vs. 132.3 µmol/L ± 26.4 in day 3 in the control group vs. 113.2 µmol/L ± 28.9 in day 1 vs. 104.3 µmol/L ± 22.1 in day 3 in the dexmedetomidine group).

Including a dropout ratio of 10%, the final total sample size is 128 patients (64 patients per group).

Statistical analysis:

The collected data will be thoroughly revised, coded, and tabulated, followed by statistical analysis. Qualitative data will be presented as numbers and percentages. Quantitative data will be represented as mean and standard deviation (SD), or median and interquartile range (IQR) according to data distribution. Chi-square test will be used to compare groups regarding non-numerical variables. Independent samples t-test of significance will be used to compare two means.

To compare proportions between two qualitative characteristics, the Chi-square (x2) test of significance will be used.

A P-value of less than 0.05 will be considered statistically significant in all analyses.

Eligibility criteria: Inclusion Criteria:

* Age \>21 years old
* Patients with sepsis who develop AKI within 48 hours during ICU stay
* Need for sedation due to the need for mechanical ventilation (MV) (both invasive and non- invasive) within 48 hours of AKI

Exclusion Criteria:

* Contraindications to dexmedetomidine including any of the following: severe bradycardia (heart rate (HR) \< 50 beats/min), sick sinus syndrome or second-to-third degree atrioventricular block unless a pacemaker is inserted
* Acute myocardial ischemia
* Mean arterial blood pressure \< 50 mmHg despite adequate resuscitation and vasopressor therapy at the time of enrollment
* Pregnancy or lactation
* Duration of dexmedetomidine infusion \< 24 hours
* Severe valvular heart disease
* Active seizures during this ICU admission requiring benzodiazepines
* Proven or suspected traumatic brain injury, intracranial hemorrhage, stroke, or spinal cord injury

Primary outcomes:
measure: Change in serum creatinine (SCr)
timeFrame: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
Secondary outcomes:
measure: Incidence of Renal Replacement therapy (RRT)
timeFrame: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
measure: Change in Sequential Organ Failure Assessment (SOFA).
timeFrame: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
measure: Incidence of agitation
timeFrame: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
measure: Incidence of bradycardia
timeFrame: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
measure: Incidence of hypotension
timeFrame: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
measure: Duration on mechanical ventilation
timeFrame: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
measure: Length of hospital and ICU stay
timeFrame: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
measure: Incidence of another organ dysfunction
timeFrame: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
measure: In-hospital mortality
timeFrame: From time of enrolment until date of death, assessed up to 1 month
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Cairo University
Study officials:
affiliation: Cairo University
name: Nirmeen A Sabry, Ph.D
role: STUDY_CHAIR
affiliation: Cairo University
name: Amany M Mohamed, Ph.D
role: STUDY_DIRECTOR
affiliation: Cairo University
name: Ramadan M Khalil, MD
role: STUDY_DIRECTOR
affiliation: Cairo University
name: Kanzy M Hassan, B. Pharm
role: PRINCIPAL_INVESTIGATOR
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