Comparative Clinical Study Between Colistin-Tigecycline Combined Therapy Versus Colistin-Meropenem Combined Therapy in Treatment of Blood Stream Infections With Multidrug-Resistant Klebsiella Pneumoniae

NCT04489459 | Unknown Phase 4

• 1 other identifier: D12019
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, comparative study is evaluating the effectiveness and adverse effects of using colistin at a loading dose of 9 million international units (MIU) followed by 4.5 MIU every 12 h (q12 h) + tigecycline at a loading dose of 100 mg followed by 50 mg every 12 h (q12 h) versus colistin + meropenem 2 g q8 h in treating blood stream infections due to multidrug-resistant (MDR) Klebsiella pneumoniae. The aims of the current study are to investigate and evaluate the therapeutic activity and side effects of Colistin-Meropenem combined therapy versus Colistin-Tigecycline combined therapy in treatment of patients with Multiple Drug Resistant (MDR)-Klebsiella pneumonia bacteraemia The primary goal is comparing 14 day mortality between critically ill patients with MDR Gram-negative Klebsiella pneumoniae infection as evaluation of the therapeutic activity of colistin - tigecycline vs. colistin - meropenem combined therapies. The secondary goal is comparing the comorbidities (nephrotoxicity, hepatotoxicity, neurotoxicity, hematological changes) between critically ill patients with MDR Gram-negative Klebsiella pneumoniae infection who will be treated with colistin - tigecycline versus colistin - meropenem combined therapies. Method: A total of 60 patients were divided into two groups (30 patients each); the first group received Intravenous colistin 9 MIU IV infusion over 2 hours loading dose followed by maintenance dose 4.5 MIU IV infusion over 2 hours q12 h plus Intravenous Tigecycline 100 mg IV infusion over 1 hour loading dose followed by maintenance dose 50 mg IV infusion over 1 hour q12 and the second group received Intravenous colistin 9 MIU IV infusion over 2 hours loading dose followed by maintenance dose 4.5 MIU IV infusion over 2 hours q12 h plus Intravenous meropenem 2 g IV infusion over 30 minutes q8 h

Conditions

Treatment of Blood Stream Infections Due to Multidrug-Resistant Klebsiella Pneumoniae

Keywords

Colistin; Tigecycline; Meropenem

Outcome Measures

Primary Outcomes (1)

• Comparing 14 day mortality between critically ill patients with MDR Gram-negative Klebsiella pneumoniae infection as evaluation of the therapeutic activity of colistin - tigecycline vs. colistin - meropenem combined therapies.

  7-14 days

Secondary Outcomes (1)

• Comparing comorbidities:nephrotoxicity,hepatotoxicity,neurotoxicity,hematological changes between critically ill patients with MDR Gram-negative Klebsiella pneumoniae infection treated with colistin-tigecycline vs colistin-meropenem

  7-14 days

Study Arms (2)

colistin-tigecycline

ACTIVE COMPARATOR

this group received Intravenous colistin 9 MIU IV infusion over 2 hours loading dose followed by maintenance dose 4.5 MIU IV infusion over 2 hours q12 h plus Intravenous Tigecycline 100 mg IV infusion over 1 hour loading dose followed by maintenance dose 50 mg IV infusion over 1 hour q12h

Drug: Colistin; Drug: Tigecycline

colistin-meropenem

ACTIVE COMPARATOR

received Intravenous colistin 9 MIU IV infusion over 2 hours loading dose followed by maintenance dose 4.5 MIU IV infusion over 2 hours q12 h plus Intravenous meropenem 2 g IV infusion over 30 minutes q8 h

Drug: Colistin; Drug: Meropenem

Interventions

Colistin DRUG

Intravenous colistin 9 MIU IV infusion over 2 hours loading dose followed by maintenance dose 4.5 MIU IV infusion over 2 hours q12 h

Also known as: polymixin B

colistin-meropenem; colistin-tigecycline

Meropenem DRUG

Intravenous meropenem 2 g IV infusion over 30 minutes q8 h

colistin-meropenem

Tigecycline DRUG

Intravenous Tigecycline 100 mg IV infusion over 1 hour loading dose followed by maintenance dose 50 mg IV infusion over 1 hour q12

colistin-tigecycline

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with blood stream infection caused by MDR K. pneumoniae, as defined by Infectious Diseases Society of America (IDSA), who were hospitalised in the general ICU, confirmed with carbapenem-resistant K. pneumoniae-positive culture results from blood sample within the previous 5 days

You may not qualify if:

• All patients without a MDR carbapenem-resistant K. pneumoniae-positive culture isolated from the blood. In addition, the following patients are excluded: patients with a Glasgow Coma Scale (GCS) score of \<9 in non-ventilated patients or \<6 in ventilated patients; patients with end-stage metastatic malignant cancer; and all terminal patients with Acute Physiology and Chronic Health Evaluation (APACHE) II or Sequential Organ Failure Assessment (SOFA) scores of \>34 or \>15, respectively, and risk of mortality \>85% or \>80% on the first day of colistin administration, respectively \[27,28\]. Moreover, patients who received i.v. colistin combination therapies for \<72 h are excluded from further analysis

Sponsors & Collaborators

• Al-Azhar University: lead

Study Sites (1)

Qasr El Ainy

Cairo, Egypt

RECRUITING

Related Publications (2)

• Daikos GL, Petrikkos P, Psichogiou M, Kosmidis C, Vryonis E, Skoutelis A, Georgousi K, Tzouvelekis LS, Tassios PT, Bamia C, Petrikkos G. Prospective observational study of the impact of VIM-1 metallo-beta-lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections. Antimicrob Agents Chemother. 2009 May;53(5):1868-73. doi: 10.1128/AAC.00782-08. Epub 2009 Feb 17.

  PMID: 19223638 BACKGROUND

• Maltezou HC, Giakkoupi P, Maragos A, Bolikas M, Raftopoulos V, Papahatzaki H, Vrouhos G, Liakou V, Vatopoulos AC. Outbreak of infections due to KPC-2-producing Klebsiella pneumoniae in a hospital in Crete (Greece). J Infect. 2009 Mar;58(3):213-9. doi: 10.1016/j.jinf.2009.01.010. Epub 2009 Feb 26.

  PMID: 19246099 BACKGROUND

MeSH Terms

Interventions

Colistin; Meropenem; Tigecycline

Intervention Hierarchy (Ancestors)

Polymyxins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Antimicrobial Cationic Peptides; Peptides; Amino Acids, Peptides, and Proteins; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Membrane Proteins; Proteins; Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Central Study Contacts

Salma Wagih Abdalla, Bachelor

CONTACT

00201100701178; salma9793@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: single-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: July 24, 2020
• First Posted: July 28, 2020
• Study Start: September 21, 2019
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: July 29, 2020

Record last verified: 2020-07

Locations

EG (1)