Drug Combinations for Bacterial Pneumonia

(REITAB-2 Trial)

Recruiting at 35 trial locations

Overseen By Yuanyuan Pan

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sinovent Pty Ltd.

Must not be taking: Valproic acid, Divalproex sodium

Disqualifiers: Immunodeficiency, Seizure disorder, Liver disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 14 days

450 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing two antibiotic combinations to treat severe lung infections acquired in hospitals or through ventilators. The antibiotics work by breaking down the bacteria's protective walls, helping to clear the infection.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications. However, you cannot take Valproic acid, divalproex sodium, or certain antibacterial, antifungal, or antiviral therapies for the infection being studied. If you have a seizure disorder requiring treatment, you may not be eligible.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take certain antibiotics, antifungal, or antiviral drugs for the infection being studied. You also cannot take Valproic acid or divalproex sodium.

What data supports the idea that Drug Combinations for Bacterial Pneumonia is an effective treatment?

The available research shows that the drug combination of imipenem/cilastatin is effective in treating bacterial pneumonia. In one study, it was found to have a 70% success rate in treating pneumonia. Another study compared imipenem/cilastatin with another antibiotic, cefotaxime, and found that both had a 90% satisfactory response rate in treating severe bacterial infections. However, imipenem/cilastatin may be more effective when combined with another drug, amikacin, to prevent resistance and improve outcomes. This combination is particularly recommended for serious infections. ^{1 2 3 4 5}

What evidence supports the effectiveness of the drug combination imipenem/cilastatin for treating bacterial pneumonia?

Research shows that imipenem/cilastatin is effective in treating severe infections, including pneumonia, with a 70% response rate. It is often used with other antibiotics like amikacin to improve effectiveness and prevent resistance. ^{1 2 3 4 5}

What safety data exists for the treatment of bacterial pneumonia with imipenem/cilastatin and related drugs?

The safety data for imipenem/cilastatin and related drugs indicate that they are generally well tolerated. In clinical studies, adverse reactions were mild or slight and transient, including general fatigue, epigastralgia, skin rash, eosinophilia, and elevated liver enzymes. The adverse reaction profile is similar to other beta-lactam antibiotics, with common side effects being phlebitis, diarrhea, nausea, and skin rash. Imipenem/cilastatin/relebactam has a safety profile consistent with imipenem/cilastatin alone. Dosage adjustments are recommended for patients with renal impairment to minimize the risk of seizures. Overall, these drugs are considered safe and effective for treating bacterial infections, including pneumonia, in adults. ^{2 3 5 6 7}

Is the drug combination of imipenem/cilastatin safe for treating bacterial infections?

Imipenem/cilastatin has been shown to be generally safe in humans, with mild and temporary side effects like fatigue, stomach pain, skin rash, and changes in liver enzymes. It is well tolerated and has a safety profile similar to other antibiotics in its class. ^{2 3 5 6 7}

Is the drug Cilastatin, Imipenem, Relebactam a promising treatment for bacterial pneumonia?

Yes, Cilastatin, Imipenem, Relebactam is a promising drug for bacterial pneumonia. It has a broad range of antibacterial activity, including effectiveness against tough bacteria that are resistant to other treatments. Studies show it works well for hospital-acquired pneumonia and can be a strong alternative to using multiple antibiotics together. ^{1 3 4 5 8}

How is the drug combination of Cilastatin, Imipenem, and Relebactam unique for treating bacterial pneumonia?

This drug combination is unique because it includes Relebactam, a β-lactamase inhibitor, which helps Imipenem work against resistant bacteria, making it effective for hospital-acquired or ventilator-associated bacterial pneumonia, especially when other treatments might fail. ^{1 4 5 8 9}

Research Team

Jason Le

Principal Investigator

Evopoint Biosciences USA, Inc.)

Eligibility Criteria

This trial is for adults with hospital-acquired or ventilator-associated bacterial pneumonia who need IV antibiotics. They must have symptoms like cough, fever, and changes on chest X-rays suggestive of pneumonia. Women of childbearing age and men with partners must agree to use birth control during the study.

Inclusion Criteria

I have a lung infection needing IV antibiotics, starting after hospital stay or ventilation.

I have symptoms like coughing, difficulty breathing, or fever.

You have high levels of white blood cells or immature neutrophils in your laboratory tests.

Exclusion Criteria

You are expected to live for less than 3 days.

I have been treated with antibiotics for a lung infection for more than 24 hours in the last 3 days.

You have abnormal test results in your blood samples taken before the study starts.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Imipenem/Cilastatin-XNW4107 or Imipenem/Cilastatin/Relebactam for the treatment of bacterial pneumonia

Up to 14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments at test-of-cure and late follow-up

Up to 31 days

Treatment Details

Interventions

• Cilastatin
• Imipenem
• Relebactam

Trial Overview The study compares two antibiotic treatments for bacterial pneumonia: Imipenem/Cilastatin combined with XNW4107 versus Imipenem/Cilastatin/Relebactam. The goal is to see if the first combination is just as effective in reducing death rates as the second.

Participant Groups

Group I: Imipenem/Cilastatin/XNW4107 Experimental Treatment 1 Intervention

Imipenem/Cilastatin 500mg/500mg in combination with XNW4107 250mg, Q6h (0.5h Infusion)

Group II: Imipenem/Cilastatin/Relebactam Active Control 1 Intervention

Imipenem/Cilastatin/Relebactam 1.25g Q6h (0.5h Infusion)

Cilastatin is already approved in United States, China for the following indications:

Approved in United States as Cilastatin for:

• Bone and joint infections
• Endocarditis
• Gynecological infection
• Infectious Diseases
• Intraabdominal Infections
• Lower Respiratory Tract Infections
• Sepsis
• Skin and skin structure infections
• Urinary Tract Infections

Approved in China as Cilastatin for:

• Bacterial Infections

Who Is Running the Clinical Trial?

Sinovent Pty Ltd.

Lead Sponsor

Trials

8

Recruited

1,500+

Evopoint Biosciences Inc.

Lead Sponsor

Trials

15

Recruited

2,800+

Findings from Research

In a study of 25 patients with severe hospital infections, imipenem/cilastatin alone had a 62% response rate, while the combination with amikacin increased the response rate to 80%, indicating that the combination may enhance treatment efficacy.

Imipenem/cilastatin was generally well tolerated, but treatment was interrupted in some cases due to resistance development or side effects, suggesting that combining it with amikacin could help prevent resistance and improve outcomes, especially in challenging infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imipenem/cilastatin in the treatment of severe hospital infections. Patoia, L., Menichetti, F., Bucaneve, G., et al.[2013]

In a study involving 20 adult patients with severe bacterial infections, imipenem/cilastatin sodium demonstrated a high efficacy, with 90% of patients showing satisfactory clinical responses and a 90% pathogen eradication rate.

Both imipenem/cilastatin and cefotaxime were found to be safe, with no major adverse effects reported in either treatment group, indicating that imipenem/cilastatin is a viable option for treating severe infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative clinical evaluation of imipenem/cilastatin vs. cefotaxime in treatment of severe bacterial infections. Stamboulian, D., Argüello, EA., Jasovich, A., et al.[2019]

Imipenem-cilastatin is a highly effective broad-spectrum antibiotic that works against a wide range of bacteria, including both gram-positive and gram-negative organisms, making it a strong option for treating serious infections.

While imipenem-cilastatin is generally safe and effective, it should be used with caution in patients with serious pseudomonal infections, as resistance can develop quickly; combining it with an aminoglycoside is recommended to prevent this issue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imipenem-cilastatin sodium, a broad-spectrum carbapenem antibiotic combination. Pastel, DA.[2018]

In a phase 3 trial involving 537 patients with hospital-acquired or ventilator-associated bacterial pneumonia, imipenem/cilastatin/relebactam demonstrated noninferior efficacy compared to piperacillin/tazobactam, with a lower day 28 all-cause mortality rate of 15.9% versus 21.3%.

Imipenem/cilastatin/relebactam was found to be a safe treatment option, with serious adverse events occurring in 26.7% of patients, which is lower than the 32.0% seen in the piperacillin/tazobactam group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Double-blind, Multicenter Trial Comparing Efficacy and Safety of Imipenem/Cilastatin/Relebactam Versus Piperacillin/Tazobactam in Adults With Hospital-acquired or Ventilator-associated Bacterial Pneumonia (RESTORE-IMI 2 Study). Titov, I., Wunderink, RG., Roquilly, A., et al.[2022]

Imipenem/cilastatin is a highly effective beta-lactam antibiotic with a broad antibacterial spectrum, effective against a wide range of gram-positive, gram-negative, and anaerobic organisms, making it suitable for various infections.

The combination of imipenem with cilastatin enhances its effectiveness by preventing its breakdown in the kidneys, and clinical trials have shown it to be as effective as combination therapies for treating serious infections like soft tissue infections and pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imipenem/cilastatin: the first carbapenem antibiotic. Lyon, JA.[2013]

In a study of 52 patients with moderate to severe infections, imipenem/cilastatin sodium (IPM/CS) demonstrated an overall clinical efficacy of 86.4%, with particularly high efficacy (93.9%) in patients who had not been previously treated with other antibiotics.

The treatment was found to be safe, with only mild and transient adverse reactions reported in six patients, indicating that IPM/CS is a useful option for managing bacterial infections in internal medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical evaluation of imipenem/cilastatin sodium in the internal medicine]. Fukuhara, H., Kusano, N., Nakamura, H., et al.[2018]

Imipenem/cilastatin/relebactam (Recarbrio™) is effective against hospital-acquired and ventilator-associated bacterial pneumonia, as well as complicated urinary tract and intra-abdominal infections, particularly in patients with limited treatment options.

In clinical trials, it was found to be noninferior to piperacillin/tazobactam and imipenem/cilastatin, and it has a safety profile similar to imipenem/cilastatin, making it a well-tolerated option for treating serious gram-negative infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imipenem/Cilastatin/Relebactam: A Review in Gram-Negative Bacterial Infections. Heo, YA.[2022]

In a multicenter trial involving 14 patients with aspiration pneumonia, imipenem/cilastatin sodium (IPM/CS) demonstrated a high efficacy rate of 78.6%, with excellent or good clinical effects in 11 out of 14 cases.

While IPM/CS was generally effective, treatment failures were associated with Pseudomonas aeruginosa, indicating that this specific organism may be resistant to the therapy and could require alternative treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical evaluation of therapy for aspiration pneumonia with imipenem/cilastatin sodium]. Kikuchi, N., Onozaki, I., Kohno, N., et al.[2018]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Imipenem/cilastatin in the treatment of severe hospital infections. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Comparative clinical evaluation of imipenem/cilastatin vs. cefotaxime in treatment of severe bacterial infections. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Imipenem-cilastatin sodium, a broad-spectrum carbapenem antibiotic combination. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

A Randomized, Double-blind, Multicenter Trial Comparing Efficacy and Safety of Imipenem/Cilastatin/Relebactam Versus Piperacillin/Tazobactam in Adults With Hospital-acquired or Ventilator-associated Bacterial Pneumonia (RESTORE-IMI 2 Study). [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Imipenem/cilastatin: the first carbapenem antibiotic. [2013]

6. Japan pubmed.ncbi.nlm.nih.gov

[Clinical evaluation of imipenem/cilastatin sodium in the internal medicine]. [2018]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Imipenem/Cilastatin/Relebactam: A Review in Gram-Negative Bacterial Infections. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

[Clinical evaluation of therapy for aspiration pneumonia with imipenem/cilastatin sodium]. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Antimicrobial management of postoperative infections in abdominal surgery: single or combination regimen? [2013]