Prospective, Randomized, Open, Controlled, Multicenter Study to Evaluate the Safety and Efficacy of the MON4STRAT Approach for Optimizing Meropenem Therapy in Intubated and Mechanically-Ventilated, Adult Patients with severe Gram-Negative lower respiratory tract infectio
- Conditions
- Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]Intubated and Mechanically-Ventilated, Adult Patients with severe Gram-Negative lower respiratory tract infection
- Registration Number
- EUCTR2018-000450-21-FR
- Lead Sponsor
- FUNDACIÓN PARA INVESTIGACIÓN BIOMÉDICA DEL HOSPITAL UNIVERSITARIO RAMÓN Y CAJA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 150
1.Males and non-pregnant, non-lactating females, 18 years of age or older;
2.Currently intubated and mechanically-ventilated subjects in the ICU;
3.a. Suspicion of Lower Respiratory Tract infection defined as at least two of the following:
•fever, defined as a tympanic/ rectal/core temperature >38,3°C , or hypothermia, defined as a rectal/core body temperature of <35,0°C;
•leukocyte count >10,000/mm3 or <4,500/mm3, or an immature neutrophil (band) count >15% regardless of the peripheral leukocyte count;
•new onset of purulent sputum or respiratory secretions, or a change in the character of sputum;
•a new or progressive pulmonary infiltrate on chest X-rays.(criterion only applicable for Spain and Belgium)
b. A new or progressive pulmonary infiltrate on chest X-rays. (only for France).
As indicated in section 2.4, in France, only patients fullfilling all the criteria for nosocomial pneumonia will be included.
4.Presence of Gram-negative organism(s) by Gram stain OR by culture of pre-therapy respiratory specimen (eg, endotracheal aspirate [ETA], bronchoalveolar lavage [BAL], or mini-BAL) OR previous colonization 48 hours before screening;
5.Initial empiric antimicrobial regimen combining meropenem with an aminoglycoside or a fluoroquinolone active on Pseudomonas, plus MRSA coverage when indicated, in accordance with the 2016 ATS/IDSA guidelines for HAP/VAP/HCAP;
6.At least two of the risk factors described as associated with HAP/VAP caused by multidrug-resistant organisms in the guidelines of the ATS/IDSA for HAP/VAP (Clin Infect Dis. 2016 Sep 1;63(5):e61-e111) and those of the ESICM/ECCMID societies (Eur Respir J. 2017 Sep 10;50(3):
•Antimicrobial therapy in the preceding two weeks;
•Current hospitalization =5 days;
•High frequency (>10%) of antibiotic resistance in the community or in the specific hospital unit, depending in particular on data issued from local official committees in line with the national epidemiological surveillance program; ;
•Immunosuppressive disease and/or therapy;
•Residence in a nursing home or extended care facility.
7.Clinical pulmonary infection score (CPIS) =6;
8.Expected to remain intubated and mechanically ventilated for =72 hours based on investigator estimate;
9.Expected to participate in the study through 28 days post first dose of meropenem;
10.Provision of written informed consent by the subject or subject’s, family member or a closerelative.
[A waiver of consent will be asked to each Ethical Committee allowing for randomizing patients when he/she is unable to give consent and no, family member or a close relative can be contacted, in accordance with law specifications of emergency consent. In that case, family member or close relative or patients will be asked to give his/her consent for continuation of the trial when his/her condition permits];
11. Affiliation to a social security system (recipient or assign)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age
Subjects who have received antibiotic therapy for Gram-negative LRT infection for = 36 hours at the time of randomization;
2.Hypersensitivity to meropenem, Hypersensitivity to any other carbapenem antibacterial agent, Severe hypersentivity (eg anaphylactic reaction, severe skin reaction) to any other type of beta-lactam antibacterial agent (e.g.penicillins or cephalosporins)
3.Subjects taking valproic/acid sodium valproat/valpromide for a seizure disorder (other anticonvulsivants are allowed)
4.Subjects who have had a left hemisphere stroke (right hemisphere affected is allowed) within five days and there is an increased risk of fatal brain oedema as indicated by a major early computerized tomography hypodensity exceeding 50% of the middle cerebral artery territory, and/or involvement of additional vascular territories;
5.Subjects who have cystic fibrosis, human immunodeficiency virus (HIV) infection with CD4 count <100 cell/mm3 (HIV testing is not required as part of this protocol), or invasive fungal infection of the lung;
6.Neutropenia (screening absolute neutrophil count <103 neutrophils/mm3);
7. Bone marrow transplant;
8.Subjects who have primary lung cancer with known endobronchial obstruction (post-operative patients after lung cancer resection are eligible for the study);
9-.Subjects with another focus of infection requiring concurrent antibiotics that would interfere with evaluation of the response to study treatment;
10 Subjects for whom therapy will require aerosolized antibiotics;
11. Subjects for whom therapy will require intermittent hemodialysis (patients treated with continuous renal replacement techniques are eligible for the study);
12. Burns greater than 40% of total body surface area;
13. Subjects with intractable septic shock (subjects requiring ongoing treatment with vasopressors will be eligible for the study if their hypotension is controlled and acidosis has resolved);
14. Rapidly fatal illness with death likely within the next 72 hours;
15. Subjects who have been on mechanical ventilation for >28 days;
16. Subjects who were previously enrolled in this study;
17. Subjects under curatorship or tutorship.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method