A Pilot Study for Optimizing Meropenem Administration in the ICU

Drug Effect Clinical Trial

— MER6  

Official title:

A Pilot Study for Optimizing Meropenem Administration in the Intensive Care Unit - Short Six Times vs Prolonged Three Times Courses Daily

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05578586
• Other study ID #: Meropenem6
• Status: Recruiting
• Phase: N/A
• Start date: December 14, 2021
• Est. completion date: December 2024

Study information

• Verified date: October 2022
• Source: Oslo University Hospital
• Contact: Ingvild Nordøy, PhD
• Phone: +4793028084
• Email: inordoy[@]ous-hf.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Can antibiotic drugs be administered faster and make acceptable serum concentrations if we give short but multiple infusions compared to long and fewer infusions? In this study we will compare giving meropenem 1 gram 6 times daily in 15 minutes infusions to the recommended 2 gram 3 times daily in 3 hours infusions. In patients in the intensive care unit, the need for intravenous access is of essence. If 6 short infusions results in the same serum concentrations as 3 long infusions, we will increase intravenous access from 15 to 22.5 hours daily.

Description:

The primary aim of this pilot study is to examine if the dosing of the antibiotic meropenem given as 1 gram 6 times daily in 15 minutes infusions can be compared to 2 grams given 3 times daily in 3 hours infusion when measuring the serum concentration above the minimum inhibitory concentration (MIC) ≥ 50 % of the time (2 mg/l). The secondary aims are - That both administration forms will result in serum concentrations above MIC ≥ 100 % of the time (2 mg/l) - Days in hospital - 30 days mortality after admittance to the ICU - Serious side-effects Five extra blood samples will be performed 24, 48 and 72 hours between two dosing intervals. The dose will be adjusted according to renal function which will be monitored daily. The patients will be supervised for adverse effects until 2 days after treatment has stopped. The study will be performed from 2021 to the end of 2024.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients = 18 years admitted to the ICU at Oslo University Hospital, Rikshospitalet and

2. who shall be treated with meropenem because of proven or suspected serious infection and

3. who give their written informed consent either directly or through next of kin Exclusion Criteria: Patients

1. with known hypersensistivity to betalactam antibiotics or

2. who use of valproat or

3. who are pregnant or

4. the lack of consent.

Related Conditions & MeSH terms

• Drug Effect

Intervention

Drug:
• Meropenem 1000 mg
given as 6 or 3 infusions in 15 minues or 3 hours.

Locations

Country	Name	City	State
Norway	Oslo University Hospital	Oslo

Sponsors (1)

Lead Sponsor	Collaborator
Oslo University Hospital

Country where clinical trial is conducted

Norway, 

References & Publications (15)

Ahmed N, Jen SP, Altshuler D, Papadopoulos J, Pham VP, Dubrovskaya Y. Evaluation of Meropenem Extended Versus Intermittent Infusion Dosing Protocol in Critically Ill Patients. J Intensive Care Med. 2020 Aug;35(8):763-771. doi: 10.1177/0885066618784264. Ep — View Citation

Binder L, Schwörer H, Hoppe S, Streit F, Neumann S, Beckmann A, Wachter R, Oellerich M, Walson PD. Pharmacokinetics of meropenem in critically ill patients with severe infections. Ther Drug Monit. 2013 Feb;35(1):63-70. doi: 10.1097/FTD.0b013e31827d496c. — View Citation

Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998 Jan;26(1):1-10; quiz 11-2. Review. — View Citation

De Waele JJ, Lipman J, Carlier M, Roberts JA. Subtleties in practical application of prolonged infusion of ß-lactam antibiotics. Int J Antimicrob Agents. 2015 May;45(5):461-3. doi: 10.1016/j.ijantimicag.2015.01.007. Epub 2015 Feb 16. — View Citation

Drusano GL. Antimicrobial pharmacodynamics: critical interactions of 'bug and drug'. Nat Rev Microbiol. 2004 Apr;2(4):289-300. Review. — View Citation

Falagas ME, Tansarli GS, Ikawa K, Vardakas KZ. Clinical outcomes with extended or continuous versus short-term intravenous infusion of carbapenems and piperacillin/tazobactam: a systematic review and meta-analysis. Clin Infect Dis. 2013 Jan;56(2):272-82. — View Citation

Mouton JW, Ambrose PG, Canton R, Drusano GL, Harbarth S, MacGowan A, Theuretzbacher U, Turnidge J. Conserving antibiotics for the future: new ways to use old and new drugs from a pharmacokinetic and pharmacodynamic perspective. Drug Resist Updat. 2011 Apr — View Citation

Petersson J, Giske CG, Eliasson E. Standard dosing of piperacillin and meropenem fail to achieve adequate plasma concentrations in ICU patients. Acta Anaesthesiol Scand. 2016 Nov;60(10):1425-1436. doi: 10.1111/aas.12808. Epub 2016 Sep 21. — View Citation

Roberts JA, Abdul-Aziz MH, Davis JS, Dulhunty JM, Cotta MO, Myburgh J, Bellomo R, Lipman J. Continuous versus Intermittent ß-Lactam Infusion in Severe Sepsis. A Meta-analysis of Individual Patient Data from Randomized Trials. Am J Respir Crit Care Med. 20 — View Citation

Roberts JA, Lipman J. Optimizing use of beta-lactam antibiotics in the critically ill. Semin Respir Crit Care Med. 2007 Dec;28(6):579-85. Review. — View Citation

Roberts JA, Paul SK, Akova M, Bassetti M, De Waele JJ, Dimopoulos G, Kaukonen KM, Koulenti D, Martin C, Montravers P, Rello J, Rhodes A, Starr T, Wallis SC, Lipman J; DALI Study. DALI: defining antibiotic levels in intensive care unit patients: are curren — View Citation

Roberts JA, Webb S, Paterson D, Ho KM, Lipman J. A systematic review on clinical benefits of continuous administration of beta-lactam antibiotics. Crit Care Med. 2009 Jun;37(6):2071-8. doi: 10.1097/CCM.0b013e3181a0054d. Review. — View Citation

Taccone FS, Laterre PF, Dugernier T, Spapen H, Delattre I, Wittebole X, De Backer D, Layeux B, Wallemacq P, Vincent JL, Jacobs F. Insufficient ß-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care. 2010;14(4):R126. doi: 1 — View Citation

Teo J, Liew Y, Lee W, Kwa AL. Prolonged infusion versus intermittent boluses of ß-lactam antibiotics for treatment of acute infections: a meta-analysis. Int J Antimicrob Agents. 2014 May;43(5):403-11. doi: 10.1016/j.ijantimicag.2014.01.027. Epub 2014 Mar — View Citation

Turnidge JD. The pharmacodynamics of beta-lactams. Clin Infect Dis. 1998 Jul;27(1):10-22. Review. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration above the minimum inhibitory concentration (MIC) = 50 % of the time (2 mg/l)	Comparing 2 ways of administering meropenem intravenously	After 24, 48 and 72 hours