Fixed-dose Amikacin for Elderly UTI

NCT04197739 | Unknown Phase 4 DMC

• 1 other identifier: RMC-0619-19
• Study Type: interventional
• Target: 200
• Locations: 0 countries
• Sites: N/A

Brief Summary

Aminoglycosides are broad-spectrum antibiotics, effective against gram-negative bacteria. Aminoglycosides urine concentration exceeds that of the plasma by up to a hundred. Their efficacy is dependent on their level above minimal inhibitory concentration (MIC); however high levels are associate with nephrotoxicity. Therefore aminoglycosides have a narrow therapeutic rang. The correlation between administrated dose and blood drug levels is hard to predict. Amikacin is a highly effective aminoglycoside, highly effective against extended spectrum beta lactamase (ESBL) bacteria. Older patients suffer from more urinary tract infection (UTIs), and have a higher frequency of infection with resistant bacteria, mainly among frail nursing home residents. Our goal is to prove that fixed low dose amikacin in the elderly patient in non-inferior to weight-adjusted treatment. Study design: A randomized prospective, open label, non-inferiority trial Study participants will be 65 years or older, who were admitted to the medical ward due to a UTI will be assigned to one of the following study arms:

1. 1.Intervention arm: in which patients will receive a fixed dose of amikacin, 500 mg, once a day.
2. 2.Comparator arm: in which patients will receive a weight adjusted dose of amikacin (15 mg/kg adjusted body weight) and continue in adjusted intervals according plasma concentrations, using the Barnes Jewish Hospital nomogram.
3. 3.Amikacin blood levels 6-14 hours following first administration, used for dose adjustment according to the nomogram. Peak amikacin blood levels, 30- 60 minutes following first or second administration.
4. 4.Urine analysis and culture upon admission to the emergency department (ER). In patients with indwelling urinary catheters, cultures will be taken following replacement with a new catheter.
5. 5.Broad serum biochemistry, complete blood count, C-reactive protein and blood cultures will be taken upon admission to the ER, two days after recruitment and at least once every three days following that, as long as the patient is receiving amikacin.

Conditions

Urinary Tract Infections; Elderly Infection

Keywords

Urinary Tract Infections; Aminoglycosides; Amikacin; Elderly

Outcome Measures

Primary Outcomes (1)

• Composite clinical failure

  A composite outcome of: clinical failure on day 5, all cause mortality on day 30, 30 days recurrent UTI.

  30 days

Secondary Outcomes (5)

• Rate of time-interval changes between amikacin doses

  5 days

• Rates of antimicrobial drug change

  7-14 days

• Clinical failure at day 5

  5 days

• Safety: acute kidney injury

  7-14 days

• Vestibular toxicity

  7-14 days

Study Arms (2)

Fixed dose

EXPERIMENTAL

patients will receive a fixed, single daily dose of amikacin, 500 mg, a day.

Drug: Amikacin

Adjusted body weight dose

ACTIVE COMPARATOR

patients will receive a weight adjusted dose of amikacin (15 mg/kg adjusted body weight) and continue in adjusted intervals according to the Barnes Jewish Hospital nomogram.

Drug: Amikacin

Interventions

Amikacin DRUG

Patients in the intervention arm will receive a fixed, single daily dose of amikacin, 500 mg, a day. Patients in the Comparator arm will receive a weight adjusted loading dose of amikacin (15 mg/kg adjusted body weight) and continue in adjusted intervals according to the Barnes Jewish Hospital nomogram

Adjusted body weight dose; Fixed dose

Eligibility Criteria

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

You may qualify if:

• A clinical diagnosis of UTI according to: pyuria, along with a new complaint of dysuria, urgency or frequency of urination, or lower abdominal pain or discomfort; AND one of the following: systemic fever, flank pain, tenderness over the costo-vertebral angle, rigors and chills, vomiting.
• Patients with moderate to severe cognitive impairment, who are unable to give reliable anamnesis, or those with permanent indwelling urinary catheter for 24 hours or more, will be considered as suffering from UTI is they present with systemic fever, pyuria and the lack of a more probable infectious cause.
• Patients who can give informed consent or those with a legal guardian who can consent on their behalf.
• Patients who received a single dose of any antimicrobial drug prior to recruitment, including amikacin.

You may not qualify if:

• Creatinine clearance \< 40 mL/sec according to the Cockcroft-Gault equation
• A known sensitivity to aminoglycosides
• A known neuromuscular pathology (including myasthenia gravis).
• Polycystic kidney disease
• A urine or blood culture positive for amikacin resistant bacteria in the 30 days prior to recruitment.
• Clinical suspicion of prostatitis, epididymitis or orchitis.
• Hemodynamical instability (mean arterial pressure of 65 mmHg or under).
• More than one dose of antimicrobial treatment that is adequate for classical UTI bacteria, unless a bacterial culture shows resistance to said treatment.
• Immunosuppressed patients; steroidal treatment will be allowed.

Sponsors & Collaborators

• Rabin Medical Center: lead

MeSH Terms

Conditions

Urinary Tract Infections

Interventions

Amikacin

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Kanamycin; Aminoglycosides; Glycosides; Carbohydrates

Central Study Contacts

Yochai Levy, MD

CONTACT

+972502991516; YOCHAILE@clalit.org.il

Yaara Leibovici Weissman, MD

CONTACT

+972544205305; YaaraLe1@clalit.org.il

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomized prospective, open label, non-inferiority trial Study participants will be 65 years or older, who were admitted to the medical ward due to a UTI will be assigned to one of the following study arms: 1. Intervention arm: in which patients will receive a fixed dose of amikacin, 500 mg, once a day. 2. Comparator arm: in which patients will receive a weight adjusted dose of amikacin (15 mg/kg adjusted body weight) and continue in adjusted intervals according plasma concentrations, using the Barnes Jewish Hospital nomogram.

Study Record Dates

• First Submitted: December 8, 2019
• First Posted: December 13, 2019
• Study Start: December 1, 2019
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: December 13, 2019

Record last verified: 2019-11