SepsisPhase 4NCT06570187
The Effect of Dexmedetomidine on the Renal Functions in Septic Critically Ill Patients
A Phase 4 study testing Dexmedetomidine and Propofol in people with Sepsis and Septic Shock, run by Cairo University at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Sepsis, Septic Shock, Acute Kidney Injury
- What is being tested?
- Dexmedetomidine and Propofol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 128 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Oct 2024to Oct 2026
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Nirmeen A Sabry, Ph.D contact
Egypt1 site, 1 recruiting
- Recruiting
Cairo University
Cairo
Kanzy M Hassan, B. Pharm, +201550793228, kanzy.mostafa.hassan@std.pharma.cu.edu.eg
Nirmeen A Sabry, Ph. D, nirmeen.sabry@pharma.cu.edu.eg
About this study
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:
- What is dexmedetomidine's effect on kidney functions?
- What is the safety and efficacy of dexmedetomidine in Sepsis-Associated Acute Kidney Injury?
Read more
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:
- Vital signs including blood pressure, body temperature, respiratory rate, heart rate, and oxygen saturation.
- Laboratory data including kidney function tests, electrolytes, complete blood count, and liver function tests.
- An electrocardiogram will be followed to check the heart's electrical activity.
- The level of alertness or agitation to avoid over and under-sedation.
- The level of organ dysfunction and mortality risks.
- Duration of mechanical ventilation.
- Duration of hospitalization.
Read the 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:
- Assessment of dexmedetomidine effect in SA-AKI through following serum creatinine (SCr) level, urinary output (UOP), and the need for renal replacement therapy (RRT).
- Assessment of dexmedetomidine safety in SA-AKI through following the incidence of new-onset bradycardia, and hypotension requiring intervention.
- 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.
- Conditions
- Sepsis, Septic Shock, Acute Kidney Injury
- Being tested
- Dexmedetomidine, Propofol
- Keywords
- Dexmedetomidine, acute kidney injury, sepsis, critically ill patients, sedation, prospective clinical trial
- Medical subject headings
- Sepsis, Shock, Septic, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Dexmedetomidine will be administered with an initial dose of 0.2 μg/kg/hour, infusion rate is to be titrated based on response for at least 24 hours.
PropofolDrug
Propofol will be administered as the comparator sedative with the standard treatment of sepsis and septic shock.
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine | Experimental | Participants will receive the standard sepsis and septic shock treatment with dexmedetomidine, which is to be administered with an initial dose of 0.2 μg/kg/hour, and the infusion rate is to be titrated based on response for at least 24 hours. Receives: Drug: Dexmedetomidine |
| Control | Active comparator | Participants will receive the standard sepsis and septic shock treatment and the standard sedatives without dexmedetomidine. Receives: Drug: Propofol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in serum creatinine (SCr)
Reduction in SCr ≥ 0.3 mg/dL within ≤ 72 hours. For patients known as acute on top of chronic kidney disease (CKD), decrease in SCr to < 1.5 times the baseline
Measured: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
Secondary outcomes (9)
Incidence of Renal Replacement therapy (RRT)
Incidence of requiring RRT during hospitalization
Measured: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
Change in Sequential Organ Failure Assessment (SOFA).
Change in SOFA from baseline
Measured: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
Incidence of agitation
Number of days free of agitation using Richmond Agitation and Sedation Scale (RASS) (0) to (-2).
Measured: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
Incidence of bradycardia
Incidence of new onset symptomatic bradycardia (defined as heart rate < 50 beats per minutes requiring intervention e.g. pacing, pharmacological support, or modification of dexmedetomidine).
Measured: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
Incidence of hypotension
Incidence of hypotension requiring an intervention (fluid administration and/or vasopressor therapy, or dose modification if the patient was already on a vasopressor).
Measured: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
Duration on mechanical ventilation
Number of days on mechanical ventilation
Measured: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
Length of hospital and ICU stay
Number of days of hospitalization
Measured: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
Incidence of another organ dysfunction
Incidence of organ dysfunction other than AKI (defined as: Coagulation, platelet count < 100,000/mm3; Hepatic, total bilirubin > 2 mg/dL; Respiratory, ration between oxygen saturation and fractional inspired oxygen SaO2/FiO2 < 315)
Measured: Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks
In-hospital mortality
Incidence of death
Measured: From time of enrolment until date of death, assessed up to 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2024
- Study start1 Oct 2024
- Primary completionOct 2026 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Cairo UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 128 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kanzy Mostafa Hassan, Cairo University
- Investigators
- Nirmeen A Sabry, Ph.D, Study chair, Cairo UniversityAmany M Mohamed, Ph.D, Study director, Cairo UniversityRamadan M Khalil, MD, Study director, Cairo UniversityKanzy M Hassan, B. Pharm, Principal investigator, Cairo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06570187
- Sponsor's protocol ID
- CL (3635)
- Status last verified
- Oct 2024
- First submitted
- 20 Aug 2024
- Last updated
- 9 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
PubMed 26903338Manrique-Caballero CL, Del Rio-Pertuz G, Gomez H. Sepsis-Associated Acute Kidney Injury. Crit Care Clin. 2021 Apr;37(2):279-301. doi: 10.1016/j.ccc.2020.11.010. Epub 2021 Feb 13.
PubMed 33752856Cobussen M, Verhave JC, Buijs J, Stassen PM. The incidence and outcome of AKI in patients with sepsis in the emergency department applying different definitions of AKI and sepsis. Int Urol Nephrol. 2023 Jan;55(1):183-190. doi: 10.1007/s11255-022-03267-5. Epub 2022 Jul 20.
PubMed 35859220Zarbock A, Koyner JL, Gomez H, Pickkers P, Forni L; Acute Disease Quality Initiative group. Sepsis-associated acute kidney injury-treatment standard. Nephrol Dial Transplant. 2023 Dec 20;39(1):26-35. doi: 10.1093/ndt/gfad142.
PubMed 37401137Devlin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pandharipande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B, Balas MC, van den Boogaard M, Bosma KJ, Brummel NE, Chanques G, Denehy L, Drouot X, Fraser GL, Harris JE, Joffe AM, Kho ME, Kress JP, Lanphere JA, McKinley S, Neufeld KJ, Pisani MA, Payen JF, Pun BT, Puntillo KA, Riker RR, Robinson BRH, Shehabi Y, Szumita PM, Winkelman C, Centofanti JE, Price C, Nikayin S, Misak CJ, Flood PD, Kiedrowski K, Alhazzani W. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018 Sep;46(9):e825-e873. doi: 10.1097/CCM.0000000000003299.
PubMed 30113379Bao N, Tang B. Organ-Protective Effects and the Underlying Mechanism of Dexmedetomidine. Mediators Inflamm. 2020 May 9;2020:6136105. doi: 10.1155/2020/6136105. eCollection 2020.
PubMed 32454792Heybati K, Zhou F, Ali S, Deng J, Mohananey D, Villablanca P, Ramakrishna H. Outcomes of dexmedetomidine versus propofol sedation in critically ill adults requiring mechanical ventilation: a systematic review and meta-analysis of randomised controlled trials. Br J Anaesth. 2022 Oct;129(4):515-526. doi: 10.1016/j.bja.2022.06.020. Epub 2022 Aug 10.
PubMed 35961815Hu H, An S, Sha T, Wu F, Jin Y, Li L, Zeng Z, Wu J, Chen Z. Association between dexmedetomidine administration and outcomes in critically ill patients with sepsis-associated acute kidney injury. J Clin Anesth. 2022 Dec;83:110960. doi: 10.1016/j.jclinane.2022.110960. Epub 2022 Oct 19.
PubMed 36272399Cioccari L, Luethi N, Bailey M, Shehabi Y, Howe B, Messmer AS, Proimos HK, Peck L, Young H, Eastwood GM, Merz TM, Takala J, Jakob SM, Bellomo R; ANZICS Clinical Trials Group and the SPICE III Investigators. The effect of dexmedetomidine on vasopressor requirements in patients with septic shock: a subgroup analysis of the Sedation Practice in Intensive Care Evaluation [SPICE III] Trial. Crit Care. 2020 Jul 16;24(1):441. doi: 10.1186/s13054-020-03115-x.
PubMed 32678054Duff S, Murray PT. Defining Early Recovery of Acute Kidney Injury. Clin J Am Soc Nephrol. 2020 Sep 7;15(9):1358-1360. doi: 10.2215/CJN.13381019. Epub 2020 Apr 1. No abstract available.
PubMed 32238366Mehta RL. Renal Recovery After Acute Kidney Injury and Long-term Outcomes: Is Time of the Essence? JAMA Netw Open. 2020 Apr 1;3(4):e202676. doi: 10.1001/jamanetworkopen.2020.2676. No abstract available.
PubMed 32282043Bai Y, Li Y, Jin J, Cheng M, Zhang S, Yang X, Xu J. Effects of early recovery of renal function on adverse renal outcomes and mortality in patients with acute kidney injury: a systematic review and meta-analysis. Int Urol Nephrol. 2024 Jul;56(7):2421-2430. doi: 10.1007/s11255-024-03974-1. Epub 2024 Mar 7.
PubMed 38451431Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):c179-84. doi: 10.1159/000339789. Epub 2012 Aug 7. No abstract available.
PubMed 22890468Hughes CG, Mailloux PT, Devlin JW, Swan JT, Sanders RD, Anzueto A, Jackson JC, Hoskins AS, Pun BT, Orun OM, Raman R, Stollings JL, Kiehl AL, Duprey MS, Bui LN, O'Neal HR Jr, Snyder A, Gropper MA, Guntupalli KK, Stashenko GJ, Patel MB, Brummel NE, Girard TD, Dittus RS, Bernard GR, Ely EW, Pandharipande PP; MENDS2 Study Investigators. Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis. N Engl J Med. 2021 Apr 15;384(15):1424-1436. doi: 10.1056/NEJMoa2024922. Epub 2021 Feb 2.
PubMed 33528922