The Effect of Dexmedetomidine on the Renal Functions in Septic Critically Ill Patients

NCT06570187 | Recruiting Phase 4 DMC

• 1 other identifier: CL (3635)
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

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. 1.What is dexmedetomidine's effect on kidney functions?
2. 2.What is the safety and efficacy of dexmedetomidine in Sepsis-Associated Acute Kidney Injury?
3. 3.Vital signs including blood pressure, body temperature, respiratory rate, heart rate, and oxygen saturation.
4. 4.Laboratory data including kidney function tests, electrolytes, complete blood count, and liver function tests.
5. 5.An electrocardiogram will be followed to check the heart's electrical activity.
6. 6.The level of alertness or agitation to avoid over and under-sedation.
7. 7.The level of organ dysfunction and mortality risks.
8. 8.Duration of mechanical ventilation.
9. 9.Duration of hospitalization.

Conditions

Sepsis; Septic Shock; Acute Kidney Injury

Keywords

Dexmedetomidine; acute kidney injury; sepsis; critically ill patients; sedation; prospective clinical trial

Outcome Measures

Primary Outcomes (1)

• 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

  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)

  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).

  Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks

• Incidence of agitation

  Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks

• Incidence of bradycardia

  Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks

• Incidence of hypotension

  Assessment will be done at time of randomization then every 48 hours through hospitalization stay, an average of 2 weeks

Study Arms (2)

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.

Drug: Dexmedetomidine

Control

ACTIVE COMPARATOR

Participants will receive the standard sepsis and septic shock treatment and the standard sedatives without dexmedetomidine.

Drug: Propofol

Interventions

Dexmedetomidine DRUG

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.

Dexmedetomidine

Propofol DRUG

Propofol will be administered as the comparator sedative with the standard treatment of sepsis and septic shock.

Control

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

Cairo University

Cairo, Egypt

RECRUITING

Related Publications (14)

• 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.

  PMID: 26903338 BACKGROUND

• Manrique-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.

  PMID: 33752856 BACKGROUND

• Cobussen 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.

  PMID: 35859220 BACKGROUND

• Zarbock 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.

  PMID: 37401137 BACKGROUND

• Devlin 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.

  PMID: 30113379 BACKGROUND

• Bao 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.

  PMID: 32454792 BACKGROUND

• Heybati 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.

  PMID: 35961815 BACKGROUND

• Hu 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.

  PMID: 36272399 BACKGROUND

• Cioccari 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.

  PMID: 32678054 BACKGROUND

• Duff 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.

  PMID: 32238366 BACKGROUND

• Mehta 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.

  PMID: 32282043 BACKGROUND

• Bai 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.

  PMID: 38451431 BACKGROUND

• Khwaja 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.

  PMID: 22890468 BACKGROUND

• Hughes 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.

  PMID: 33528922 BACKGROUND

MeSH Terms

Conditions

Sepsis; Shock, Septic; Acute Kidney Injury

Interventions

Dexmedetomidine; Propofol

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Nirmeen A Sabry, Ph.D

  Cairo University

  STUDY CHAIR

• Amany M Mohamed, Ph.D

  Cairo University

  STUDY DIRECTOR

• Ramadan M Khalil, MD

  Cairo University

  STUDY DIRECTOR

• Kanzy M Hassan, B. Pharm

  Cairo University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kanzy Hassan, B. Pharm

CONTACT

+201550793228; kanzy.mostafa.hassan@std.pharma.cu.edu.eg

Nirmeen A Sabry, Ph.D

CONTACT

nirmeen.sabry@pharma.cu.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Pharmacist

Model Details: 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.

Study Record Dates

• First Submitted: August 20, 2024
• First Posted: August 26, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: October 9, 2024

Record last verified: 2024-10

Locations

EG (1)