Tobramycin Administered at the Beginning of Dialysis

NCT03904836 | Completed Phase 1

• 1 other identifier: 2019-1619
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate whether the administration of a full tobramycin dose (5 mg/kg) during the first 30 minutes of a hemodialysis session provides favorable pharmacokinetic parameters in subjects with end-stage renal disease who are suspected or has been diagnosed with Gram-negative rod-type infection. It is anticipated that the administration of a single 5 mg/kg dose of tobramycin during the first 30 minutes of a hemodialysis session will achieve an optimal ratio of maximum tobramycin concentration to minimal inhibitory concentration (Cmax/CMI) of 8 to 10 while limiting the accumulation (trough \< 2 mg/L before the next hemodialysis session) in end-stage renal disease subjects requiring intermittent hemodialysis sessions.

Conditions

Renal Dialysis; Renal Failure, Chronic

Keywords

Chronic Renal Diseases; Kidney Failure, Chronic; Renal Failure, Chronic; Tobramycin; Aminoglycosides; Pharmacokinetics; Infection; Anti-Bacterial Agents; Antibiotics; Renal Insufficiency, Chronic

Outcome Measures

Primary Outcomes (1)

• Ratio of maximum tobramycin concentration to minimal inhibitory concentration

  In subjects receiving a single 5 mg/kg tobramycin dose during the first 30 minutes of a hemodialysis session, to determine the proportion of subjects in whom the maximum concentration is greater than or equal to 8 times that of the minimal inhibitory concentration

  The timeframe for data collection for this outcome is 48 hours to 72 hours

Secondary Outcomes (7)

• Tobramycin trough level

  The timeframe for data collection for this outcome is 48 hours to 72 hours

• Residual clearance

  The timeframe for data collection for this outcome is 48 hours to 72 hours

• Clearance associated with hemodialysis

  The timeframe for data collection for this outcome is 48 hours to 72 hours

• Volume of distribution

  The timeframe for data collection for this outcome is 48 hours to 72 hours

• Total area under the curve

  The timeframe for data collection for this outcome is 0 to 48 or 72 hours (depending on time between the two dialysis)

Study Arms (1)

Tobramycin

EXPERIMENTAL

Subjects with end-stage renal disease who have been involved in an intermittent hemodialysis program and who have suspected or diagnosed Gram-negative rod-type infection

Drug: Tobramycin

Interventions

Tobramycin DRUG

5 milligrams per kilogram intravenous for one dose

Tobramycin

Eligibility Criteria

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

You may qualify if:

• Subjects aged 18 and over;
• Subjects with end-stage renal disease who are on an intermittent hemodialysis program (three times a week, 3-4 hours) at the Hôpital Maisonneuve-Rosemont hemodialysis unit for at least one month;
• Subjects with suspicion or diagnosis of Gram-negative rod-type bacteria infection for which an antibiotic is prescribed;
• Subjects able to consent to the study (consent form read and signed by the subject).

You may not qualify if:

• Contraindication or possible medical hazard related to the administration of tobramycin or to any ingredient in the formulation (e.g. sulphites), such as severe allergies or aminoglycoside-reported previous intolerances;
• Variable residual renal function (e.g. acute or transient renal failure requiring occasional hemodialysis sessions, post-renal transplantation);
• Conditions sensitive to the side effects of tobramycin (e.g. history of myasthenia gravis, Parkinson's disease, vestibular or auditory disorder);
• Subjects with impaired volume of distribution (ie, severe burns \[\> 20%\], significant ascites, decompensation for acute heart failure requiring hospitalization, admission to the critical care unit, cystic fibrosis, morbid obesity \[dry weight greater than 50% of ideal weight\]);
• Pregnant or breastfeeding women;
• Unstable hemodynamic status (risk of not tolerating / completing a 3-4 hour dialysis session);
• Recent treatment with an aminoglycoside (\<1 month);
• Participation in another research protocol;
• Inability to give free and informed consent.

Sponsors & Collaborators

• Maisonneuve-Rosemont Hospital: lead

Study Sites (1)

Maisonneuve-Rosemont Hospital

Montreal, Quebec, H1T 2M4, Canada

Location

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MeSH Terms

Conditions

Kidney Failure, Chronic; Renal Insufficiency, Chronic; Infections

Interventions

Tobramycin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nebramycin; Kanamycin; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Jean-Philippe Lafrance, MD

  Maisonneuve-Rosemont Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: April 5, 2019
• Study Start: January 31, 2019
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: February 26, 2021

Record last verified: 2021-02

Locations

CA (1)