Targeted Antibiotic Therapy for Pneumonia

Recruiting at 11 trial locations

Overseen By Michael Rothberg, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The Cleveland Clinic

Disqualifiers: ICU admission, Comfort care, Cystic fibrosis, Recent discharge, Known pathogen, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days

12500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores better ways to treat pneumonia by reducing broad antibiotic use. Researchers are testing two strategies: rapid diagnostic testing, which may involve the antibiotic combination Meropenem and vaborbactam (also known as Carbavance or Vabomere), to quickly identify the pneumonia cause, and pharmacist-led de-escalation to adjust treatments once a patient improves. Participants will join one of four groups to determine the most effective approach. People diagnosed with pneumonia, admitted to participating hospitals, and not recently in the ICU or discharged from another hospital, might be suitable for this trial. As an unphased trial, this study allows participants to contribute to innovative pneumonia treatment strategies.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that when pharmacists reduced certain medications, it was effective and did not harm patients. This indicates the method was safe and well-tolerated. The study showed that reducing some antibiotics did not impact patients' recovery.

Research on quick tests for infections shows they can identify illnesses faster and guide treatment. While specific safety details for these tests aren't available, they typically involve standard lab work, which is generally safe.

Both methods aim to enhance patient care by making treatments more precise, and current evidence suggests they are safe for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these approaches to treating pneumonia because they aim to personalize and optimize care in ways that standard treatments don't. Rapid diagnostic testing quickly identifies specific pathogens causing the infection, allowing for targeted treatment rather than the broad-spectrum antibiotics typically used. This specificity can reduce unnecessary antibiotic use and combat resistance. Meanwhile, pharmacist-led de-escalation involves a clinical pharmacist actively reviewing patient data to determine when it's safe to reduce antibiotic use. This personalized oversight helps ensure patients receive just the right amount of medication, potentially improving outcomes and reducing side effects. Together, these methods could revolutionize pneumonia treatment by making it more precise and efficient.

What evidence suggests that this trial's treatments could be effective for pneumonia?

In this trial, participants will be assigned to different treatment arms to evaluate targeted antibiotic therapies for pneumonia. Research has shown that quick tests, which participants in the Rapid Diagnostic Testing (RDT) arm will undergo, can rapidly identify the germs causing pneumonia. This enables doctors to start the right treatment faster, improving patient health. Studies have found that using these tests can enhance the timing of treatment, resulting in higher recovery rates and shorter hospital stays.

In the Pharmacist-led de-escalation arm, pharmacists will suggest changes to simplify antibiotic treatments when they are no longer needed. Research supports this method, showing it leads to shorter hospital stays and helps avoid unnecessary antibiotic use. Doctors typically accept these suggestions, which can reduce overall antibiotic use and improve patient care. Additionally, some participants will receive both RDT and Pharmacist-led de-escalation to assess the combined effect. ^{1 6 7 8 9}

Who Is on the Research Team?

Michael Rothberg, M.D.

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

This trial is for adults over 18 with pneumonia, admitted to a participating hospital without intensive care in the first 24 hours, not on comfort care only, without cystic fibrosis or recent discharge from acute care. It excludes those known to have a specific pathogen causing their illness.

Inclusion Criteria

Admitted to a participating (i.e. enrolled and randomized) hospital

I have been diagnosed with pneumonia.

Exclusion Criteria

I was discharged from the hospital within the last week.

I was admitted to the ICU within 24 hours of being hospitalized.

I am only receiving treatments to ease symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rapid diagnostic testing and/or pharmacist-led de-escalation for community-acquired pneumonia

21 days

Daily monitoring by clinical pharmacist on weekdays

Follow-up

Participants are monitored for safety and effectiveness after treatment, including infection with resistant organisms and 30-day readmission

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Pharmacist-led de-escalation
• Rapid Diagnostic Testing

Trial Overview The study tests if rapid diagnostic testing and pharmacist-led de-escalation can reduce broad-spectrum antimicrobial use in community-acquired pneumonia. It's a 3-year trial with four groups: one gets rapid tests, another gets pharmacist help, one gets both, and the last follows usual care.

How Is the Trial Designed?

Group I: Rapid diagnostic testing (RDT) Active Control 1 Intervention

Rapid diagnostic testing: Eligible patients at hospitals randomized to this arm will undergo testing for viral pathogens (from November-April) and pneumococcal UAT and procalcitonin testing. If the patient is not being admitted to the ICU, and the patient has an admitting diagnosis of pneumonia, the form will append orders for viral testing, UAT and procalcitonin testing to providers in hospitals randomized to receive it.

Group II: Pharmacist-led de-escalation Active Control 1 Intervention

Pharmacist-led de-escalation: Another CDSS algorithm will identify CAP patients who meet study criteria and have negative culture results for \> 48 hours and generate a list for the clinical pharmacist, who will be a member of the study team. The alerts will be audited by the pharmacist daily on weekdays at a centralized location. The pharmacist will attempt to determine whether each patient is clinically stable. The validated measures of clinical stability in patients with CAP are a) resolved vital sign abnormalities b) normal mental status c) ability to eat. If the patient appears stable, the pharmacist will communicate their recommendations for de-escalation to the clinical providers via a phone call or page.

Group III: Rapid diagnostic testing (RDT) and Pharmacist-led de-escalation Active Control 2 Interventions

Rapid diagnostic testing: Eligible patients at hospitals randomized to this arm will undergo testing for viral pathogens (from November-April) and pneumococcal UAT and procalcitonin testing. If the patient is not being admitted to the ICU, and the patient has an admitting diagnosis of pneumonia, the form will append orders for viral, UAT and procalcitonin testing to providers in hospitals randomized to receive it. Pharmacist-led de-escalation: Another CDSS algorithm will identify CAP patients who meet study criteria and have negative culture results for \>48-hours and generate a list for the clinical pharmacist, who will be a member of the study team. The alerts will be audited by the pharmacist daily on weekdays at a centralized location. The pharmacist will attempt to determine whether each patient is clinically stable. If the patient appears stable, the pharmacist will communicate their recommendations for de-escalation to the clinical providers via a phone call or page.

Group IV: Usual care (no intervention) Active Control 1 Intervention

Usual care

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

Meropenem-vaborbactam is effective against complicated urinary tract infections and acute pyelonephritis caused by carbapenem-resistant Enterobacteriaceae, as shown in the Phase III trial TANGO I.

The drug is safe, well tolerated, and has better pharmacokinetic and pharmacodynamic profiles compared to other antibiotics targeting the same resistant bacteria, making it a valuable option for treating infections caused by K. pneumoniae carbapenemase-producing CRE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meropenem-vaborbactam: a new weapon in the war against infections due to resistant Gram-negative bacteria. Patel, TS., Pogue, JM., Mills, JP., et al.[2019]

Cabazitaxel, abiraterone, and enzalutamide show comparable overall survival outcomes for patients with metastatic castrate-resistant prostate cancer, with no significant differences found in median survival rates among the treatments.

However, cabazitaxel is associated with a higher risk of certain adverse events, such as anemia, diarrhea, and pyrexia, compared to abiraterone and enzalutamide, indicating a need for careful consideration of side effects when choosing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect treatment comparison of cabazitaxel for patients with metastatic castrate-resistant prostate cancer who have been previously treated with a docetaxel-containing regimen. Fryzek, JP., Reichert, H., Summers, N., et al.[2021]

Meropenem-Vaborbactam (Vabomere) is effective against infections caused by carbapenem-resistant Enterobacteriaceae, showing promising results in clinical settings.

The combination of Meropenem and Vaborbactam enhances the efficacy of treatment by overcoming resistance mechanisms, making it a valuable option for patients with limited antibiotic choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meropenem-Vaborbactam (Vabomere™): Another Option for Carbapenem-Resistant Enterobacteriaceae. Lee, Y., Kim, J., Trinh, S.[2020]

Recent advancements in the treatment of castration-resistant prostate cancer (CRPC) have introduced four new therapies that improve patient outcomes, emphasizing the importance of understanding the disease's biology and the role of the androgen receptor as a therapeutic target.

Patient selection, timing of therapy, and cost-effectiveness are critical factors in the management of CRPC, as the introduction of novel treatments, including immunotherapy and specific androgen receptor inhibitors, has changed the standard care approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel agents for the management of castration-resistant prostate cancer. Haddad, H., Garcia, JA.[2012]

Multidrug resistance (MDR) in Pseudomonas aeruginosa poses a significant challenge for selecting effective antibiotic treatments, necessitating careful consideration of both empiric and definitive therapy options.

Newer antibiotics like ceftolozane-tazobactam and ceftazidime-avibactam show promise against MDR-PSA, but more clinical data is needed to establish their effectiveness in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approach to the Treatment of Patients with Serious Multidrug-Resistant Pseudomonas aeruginosa Infections. O'Donnell, JN., Bidell, MR., Lodise, TP.[2021]

In a study of 70 patients with ventilator-associated pneumonia (VAP), switching to trimethoprim-sulfamethoxazole (TMP-SMX) from β-lactam antibiotics did not lead to higher mortality rates at 30 days or at the end of treatment, indicating its safety as a treatment option.

The findings suggest that using TMP-SMX as a de-escalation strategy from broader-spectrum antibiotics is a viable approach that warrants further investigation in larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trimethoprim-sulfamethoxazole as de-escalation in ventilator-associated pneumonia: a cohort study subanalysis. Strazzulla, A., Postorino, MC., Youbong, T., et al.[2021]

Meropenem-vaborbactam is an effective treatment for complicated urinary tract infections caused by carbapenem-resistant Enterobacteriaceae (CRE), particularly those producing Klebsiella pneumoniae carbapenemase (KPC), showing higher treatment success rates compared to traditional therapies.

This novel combination not only has lower toxicity but also presents a stronger defense against developing antimicrobial resistance, making it a preferred option for managing serious infections caused by KPC-producing CRE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meropenem-vaborbactam for adults with complicated urinary tract and other invasive infections. Albin, OR., Patel, TS., Kaye, KS.[2019]

Vaborem, a combination of vaborbactam and meropenem, is effective against Carbapenem-resistant Enterobacterales (CRE) infections, particularly those caused by Klebsiella pneumoniae carbapenemase (KPC), and is expected to improve patient outcomes by reducing treatment failures and the need for chronic renal replacement therapy.

In a cost-effectiveness analysis based on a 5-year model in Italy, Vaborem demonstrated a gain of 0.384 quality-adjusted life years (QALYs) at an incremental cost of €3549, resulting in a cost-effectiveness ratio of €9246/QALY, indicating it is a cost-effective treatment option compared to the best available therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of Vaborem in Carbapenem-resistant Enterobacterales (CRE) -Klebsiella pneumoniae infections in Italy. Mennini, FS., Gori, M., Vlachaki, I., et al.[2021]

In a phase I trial involving 22 patients with hormone-resistant prostate cancer, the combination of docetaxel (DTX) and zoledronic acid (ZOL) administered bi-weekly showed promising anti-tumor activity, particularly with the sequence of DTX followed by ZOL.

Sequence A (DTX followed by ZOL) resulted in disease control in 6 out of 9 patients and a decrease in biological markers, while sequence B did not demonstrate any anti-tumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metronomic administration of zoledronic acid and taxotere combination in castration resistant prostate cancer patients: phase I ZANTE trial. Facchini, G., Caraglia, M., Morabito, A., et al.[2020]

In a post hoc analysis of the TANGO-II trial, meropenem-vaborbactam (MV) showed a 42.9% absolute increase in clinical cure rates compared to best available therapy (BAT) for patients with KPC-producing Enterobacteriaceae infections, indicating its superior efficacy.

MV was associated with fewer adverse events and a 29.0% reduction in mortality, suggesting it is a well-tolerated and effective treatment option for serious carbapenem-resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Meropenem-Vaborbactam Versus Best Available Therapy for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Patients Without Prior Antimicrobial Failure: A Post Hoc Analysis. Bassetti, M., Giacobbe, DR., Patel, N., et al.[2020]

Citations

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Pharmacist-led stewardship for community-acquired pneumonia Conclusion: Clinicians were generally receptive to ID pharmacist-led CAP recommendations with an overall acceptance rate of 72%. Prescribers ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2667276625000812

Comparison of length of stay in community-acquired ... These findings support the use of pharmacy-led de-escalation protocols to optimize patient outcomes through IV to PO interchange.

3. wcujhw.scholasticahq.com wcujhw.scholasticahq.com/article/141003-pharmacist-driven-de-escalation-of-empiric-mrsa-therapy-based-on-nasal-pcr-in-pneumonia-patients

Pharmacist-driven De-Escalation of Empiric MRSA Therapy ... The objectives of this study were to assess the impact of pharmacist-led de-escalation of MRSA-targeted antibiotics in pneumonia using negative MRSA nasal PCR.

4. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07615-3

Reducing antimicrobial overuse through targeted therapy for ... Our study aims to determine whether identifying an etiological agent early and pharmacist-led de-escalation (calling attention to negative cultures) can safely ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11574597/

Evaluation of interventions led by pharmacists in antimicrobial ... The outcomes reported included reduction in antimicrobial consumption, cost reduction, shortening of the duration of antimicrobial therapy, and de-escalation.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11890093/

Carbapenem de-escalation as an antimicrobial stewardship ... Carbapenem de-escalation led to a reduction in carbapenem use by 2 to 5 days and was not associated with negative outcomes.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05568654

Study Details | NCT05568654 | Reducing Antimicrobial ... Pharmacist-led de-escalation: Another CDSS algorithm will identify CAP patients who meet study criteria and have negative culture results for >48-hours and ...

8. mdpi.com mdpi.com/2079-6382/14/1/29

Comparative Outcomes of Meropenem–Vaborbactam vs. ... In this cohort of hospitalized patients treated with either MEV or CZA for their infectious syndrome, MEV was associated with lower adjusted hospital mortality.

9. academic.oup.com academic.oup.com/ofid/article/7/3/ofaa051/5740215

Real-world Multicenter Analysis of Clinical Outcomes and ... Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections.