Clinical trial • Not applicable • Infectious Disease

PIVMECILLINAM HYDROCHLORIDE for Gram-negative bacteremia

Not applicable trial of PIVMECILLINAM HYDROCHLORIDE for Gram-negative bacteremia.

Overview

Trial Therapeutic Area
Infectious Disease
Trial Disease
Gram-negative bacteremia
Trial Stage
Not applicable
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
01-07-2024
First CTIS Authorization Date
25-07-2024

Trial design

Randomised, open-label, intervention arm: 5 days of antibiotic treatment. control arm: minimum of 7 days or more of antibiotic treatment. specific antibiotic choice is per local standard and multiple authorised antibiotics are permitted (examples listed in imps include: nitrofurantoin; trimethoprim; ciprofloxacin (oral and infusion formulations); piperacillin/tazobactam; meropenem; ertapenem; ampicillin; amoxicillin/clavulanic acid (bioclavid); ceftazidime; gentamicin (hexamycin); tobramycin (nebcina); sulfamethoxazole/trimethoprim; sulfametizol; selexid (pivmecillinam/mecillinam)). Not applicable trial across 7 sites in Denmark.

Randomised
Yes
Open Label
Yes
Comparator
Intervention arm: 5 days of antibiotic treatment. Control arm: minimum of 7 days or more of antibiotic treatment. Specific antibiotic choice is per local standard and multiple authorised antibiotics are permitted (examples listed in IMPs include: Nitrofurantoin; Trimethoprim; Ciprofloxacin (oral and infusion formulations); Piperacillin/Tazobactam; Meropenem; Ertapenem; Ampicillin; Amoxicillin/clavulanic acid (Bioclavid); Ceftazidime; Gentamicin (Hexamycin); Tobramycin (Nebcina); Sulfamethoxazole/Trimethoprim; Sulfametizol; Selexid (pivmecillinam/mecillinam)).
Target Sample Size
380
Trial Duration For Participant
90

Eligibility

Recruits 380 No vulnerable population selected (isVulnerablePopulationSelected=false). Inclusion requires 'Oral and written informed consent' and only adults (Age >18 years) are eligible..

Pregnancy Exclusion
Pregnancy or breastfeeding
Vulnerable Population
No vulnerable population selected (isVulnerablePopulationSelected=false). Inclusion requires 'Oral and written informed consent' and only adults (Age >18 years) are eligible.

Inclusion criteria

  • {"criterion_text":"- Age >18 years\n- Blood culture positive for Gram-negative bacteria\n- Evidence of urinary tract source of infection (positive urine culture or at least one clinical symptom compatible with urinary tract infection)\n- Antibiotic treatment with antimicrobial activity to Gram-negative bacteria administrated within 12 hours of first blood culture\n- Temperature <37.8°C at randomization\n- Clinically stabile at randomization (systolic blood pressure > 90 mm Hg, heart rate <100 beats/min., respiratory rate <24/minute, peripheral oxygen saturation > 90 %)\n- Oral and written informed consent"}

Exclusion criteria

  • {"criterion_text":"- Antibiotic treatment (>2 day) with antimicrobial activity to Gram-negative bacteria within 14 days of inclusion\n- Gram-negative bacteremia within 30 days of blood culture\n- Immunosuppression (Untreated HIV-infection, Neutropenia (absolute neutrophil count < 1.0 x 109/l), Untreated terminal cancer, Receiving immunosuppressive agents (ATC-code L04A), Corticosteroid treatment (≥20 mg/day prednisone or the equivalent for >14 days) within the last 30 days, Chemotherapy within the last 30 days, Immunosuppressed after solid organ transplantation, Asplenia)\n- Polymicrobial growth in blood culture\n- Bacteremia with non-fermenting Gram-negative bacteria (Acinetobacter spp, Burkholderia spp, Pseudomonas spp), Brucella spp, or Fusobacterium spp\n- Failure to remove source of infection within 72 hours of first blood culture (e.g. change of catheter á demeure)\n- Pregnancy or breastfeeding"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 90-day survival without clinical or microbiological failure to treatment","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Mortality (timeframe 14, 30 and 90 days)\n- Total duration of antibiotic treatment (timeframe 90 days)\n- Type of antibiotic treatment (timeframe 90 days)\n- Duration of antibiotic treatment (timeframe 90 days)\n- Total length of hospital stay (timeframe 90 days)\n- Hospital re-admission\n- Antibiotic adverse events (timeframe 30 and 90 days)\n- Use of antimicrobials after discharge (timeframe 90 days)\n- Severe adverse events (timeframe 90 days)\n- Acute kidney injury (timeframe 90 days)\n- Clostridioides difficile infection - Number of participants with Clostridioides difficile infection (timeframe 90 days)\n- Multidrug-resistance organism: Multidrug-resistance organism defined as identification of resistant bacteria in a clinical specimen obtained only from a clinical infection. (timeframe 90 days)","definition_or_measurement_approach":"Timeframes provided in parentheses for applicable endpoints (e.g., mortality measured at 14, 30 and 90 days; antibiotic adverse events at 30 and 90 days; most others at 90 days). Multidrug-resistance organism defined as identification of resistant bacteria in a clinical specimen obtained only from a clinical infection."}

Recruitment

Planned Sample Size
380
Recruitment Window Months
78
Consent Approach
Oral and written informed consent is required from participants; only adults (Age >18 years) may consent. Subject information and informed consent form documents are listed (e.g., 'GNB5 Skriftlig deltagerinformation AHH'). No assent process or materials for under-18s are described. Languages of consent documents are not specified in the available data.

Geography

Total Number Of Sites
7
Total Number Of Participants
380

Denmark

Earliest CTIS Part Ii Submission Date
12-07-2024
Latest Decision Or Authorization Date
25-07-2024
Processing Time Days
13
Number Of Sites
7
Number Of Participants
380

Sites

Site Name
Gentofte Hospital
Department Name
Infectious Diseases
Contact Person Name
Pernille Ravn
Contact Person Email
pernille.ravn@regionh.dk
Site Name
Hvidovre Hospital
Department Name
Infectious Diseases
Contact Person Name
Fatimah Al-Zergani
Contact Person Email
fatialz93@gmail.com
Site Name
Nordsjællands Hospital
Department Name
Infectious Diseases
Contact Person Name
Birgitte Lindegaard
Site Name
Odense University Hospital
Department Name
Infectious Diseases
Contact Person Name
Isik Johansen
Contact Person Email
isik.somuncu.johansen@rsyd.dk
Site Name
Aalborg University Hospital
Department Name
Infectious Diseases
Contact Person Name
Karina Frahm Kirk
Contact Person Email
kfk@rn.dk
Site Name
Herlev og Gentofte Hospital
Department Name
Infectious Diseases
Contact Person Name
Suzanne Lunding
Contact Person Email
suzanne.lunding01@regionh.dk
Site Name
Bispebjerg Hospital
Department Name
Infectious Diseases
Contact Person Name
Jesper Andreas Knudsen

Sponsor

Primary sponsor

Full Name
Region Hovedstaden
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Denmark

Third parties

  • {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"Sponsor duties (code 1); contact email: gcp-enheden.bispebjerg-frederiksberg-hospitaler@regionh.dk","organisation_type":"Hospital/Clinic/Other health care facility"}

Investigational products

Investigational Product Name
Selexid
Active Substance
PIVMECILLINAM HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised (marketingAuthNumber: 09131)
Maximum Dose
1200 mg per day
Investigational Product Name
Selexid
Active Substance
PIVMECILLINAM HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised (marketingAuthNumber: 45237)
Maximum Dose
2400 mg per day
Investigational Product Name
Ciprofloxacin Fresenius Kabi
Active Substance
CIPROFLOXACIN
Modality
Small molecule
Routes Of Administration
IV INJECTION, IV INFUSION
Route
IV INJECTION, IV INFUSION
Authorisation Status
Authorised (marketingAuthNumber: 38748)
Maximum Dose
800 mg per day
Investigational Product Name
Ampicillin "PCD"
Active Substance
AMPICILLIN
Modality
Small molecule
Routes Of Administration
SOLUTION FOR INJECTION
Route
SOLUTION FOR INJECTION/INFUSION
Authorisation Status
Authorised (marketingAuthNumber: 06941 / 06940)
Maximum Dose
8 g per day
Investigational Product Name
Meropenem "Stada"
Active Substance
MEROPENEM ANHYDROUS
Modality
Small molecule
Routes Of Administration
SOLUTION FOR INJECTION OR INFUSION
Route
SOLUTION FOR INJECTION/INFUSION
Authorisation Status
Authorised (marketingAuthNumber: 48869 / 48870)
Maximum Dose
1500 mg per day (or 3 g per day in some formulations)
Investigational Product Name
Sulfametizol ”Alternova”
Active Substance
SULFAMETHIZOLE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised (marketingAuthNumber: 16510)
Maximum Dose
2000 mg per day
Investigational Product Name
Selexid (solution for injection)
Active Substance
MECILLINAM
Modality
Small molecule
Routes Of Administration
SOLUTION FOR INJECTION
Route
SOLUTION FOR INJECTION
Authorisation Status
Authorised (marketingAuthNumber: 13525)
Maximum Dose
3 g per day
Investigational Product Name
Bioclavid
Active Substance
AMOXICILLIN, CLAVULANIC ACID
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised (marketingAuthNumber: 18925)
Maximum Dose
1500 mg per day
Investigational Product Name
Piperacillin/Tazobactam "Stragen"
Active Substance
PIPERACILLIN, TAZOBACTAM
Modality
Small molecule
Routes Of Administration
SOLUTION FOR INFUSION
Route
SOLUTION FOR INFUSION
Authorisation Status
Authorised (marketingAuthNumber: 40525 / 40526)
Maximum Dose
8 g to 16 g per day (product entries vary)
Investigational Product Name
Ciprofloxacin "HEXAL" (tablet)
Active Substance
CIPROFLOXACIN
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised (marketingAuthNumber: 33094 / 33095 / 33096)
Maximum Dose
1000-1500 mg per day depending on formulation
Investigational Product Name
Ciprofloxacin (infusion)
Active Substance
CIPROFLOXACIN
Modality
Small molecule
Routes Of Administration
IV INJECTION, IV INFUSION
Route
IV INJECTION, IV INFUSION
Authorisation Status
Authorised (marketingAuthNumber: 38748)
Maximum Dose
800 mg per day (infusion product entry)
Investigational Product Name
Ceftazidim "Fresenius Kabi"
Active Substance
CEFTAZIDIME
Modality
Small molecule
Routes Of Administration
SOLUTION FOR INJECTION
Route
SOLUTION FOR INJECTION
Authorisation Status
Authorised (marketingAuthNumber: 42731)
Maximum Dose
3 g per day
Investigational Product Name
Hexamycin (Gentamicin)
Active Substance
GENTAMICIN
Modality
Small molecule
Routes Of Administration
SOLUTION FOR INJECTION
Route
SOLUTION FOR INJECTION
Authorisation Status
Authorised (marketingAuthNumber: 11812)
Maximum Dose
5 mg/Kg per day (as listed)
Investigational Product Name
Ertapenem Fresenius Kabi
Active Substance
ERTAPENEM SODIUM
Modality
Small molecule
Routes Of Administration
SOLUTION FOR INFUSION
Route
SOLUTION FOR INFUSION
Authorisation Status
Authorised (marketingAuthNumber: 57307)
Maximum Dose
1 g per day
Investigational Product Name
Sulfametoxazol med trimetoprim SAD
Active Substance
SULFAMETHOXAZOLE, TRIMETHOPRIM
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised (marketingAuthNumber: 16511)
Maximum Dose
1920 mg per day
Investigational Product Name
Nebcina (Tobramycin)
Active Substance
TOBRAMYCIN
Modality
Small molecule
Routes Of Administration
IV INJECTION, IV INFUSION
Route
IV INJECTION, IV INFUSION
Authorisation Status
Authorised (marketingAuthNumber: 06331)
Maximum Dose
5 mg/Kg per day (product entry)
Investigational Product Name
Nitrofurantoin "EQL Pharma"
Active Substance
NITROFURANTOIN
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised (marketingAuthNumber: 7397)
Maximum Dose
400 mg per day
Investigational Product Name
Trimopan
Active Substance
TRIMETHOPRIM
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised (marketingAuthNumber: 09204)
Maximum Dose
400 mg per day

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