A Study to Evaluate Safety and Effectiveness of Bacteriophage Treatment in Patients with Prosthetic Joint Infections

Overview

About this study

The primary objectives of this study are to evaluate the safety and tolerability of intra-articular (IA) and intravenous (IV) phage therapy with antibiotics in adult patients with chronic prosthetic knee or hip infection, and to evaluate the effectiveness of IA and IV phage therapy with antibiotics in comparison with that of two-stage exchange arthroplasty in adult patients with chronic prosthetic knee or hip infection.

 

 

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Males or females ≥18 years of age who reside in the US.
  • Candidate for a two-stage exchange arthroplasty due to chronic PJI of the hip or knee following initial arthroplasty. The patient may have had one prior DAIR procedure.
  • No anticipated need for antibiotic treatment for PJI (aside from that allowed under this protocol) or for other infections so as not to confound culture results required for this study.
  • Chronic PJI (defined as onset of symptoms > 4 weeks following the initial joint replacement and persistence of symptoms for at least 3 weeks) caused by 1 or 2 of the following organisms:  Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Enterococcus faecium, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and/or Klebsiella pneumoniae.
  • No more than 2 bacterial pathogens and each must be sensitive to at least one available PhageBank phage and to a commercially available antibiotic based on the arthrocentesis obtained at screening.
  • Female patients of childbearing potential and male patients who are not sterile whose female partners are of childbearing potential must agree to use an acceptable method of contraception up through 30 days after the last dose of phage therapy for patients in Arm 1 (phage therapy in conjunction with antibiotic treatment) and per institutional practices for patients in Arm 2 (SOC). Male and female patients in Arm 1 must agree not to donate sperm or eggs, respectively, through 30 days after the last dose of phage therapy. Females of childbearing potential include any female who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (to be considered postmenopausal, the patient must have had amenorrhea for > 12 consecutive months). Females who are using oral, implanted, or injectable contraceptive hormones, an intrauterine device, barrier methods (diaphragm, condoms, spermicide) to prevent pregnancy, practicing abstinence, or whose partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential.

Exclusion Criteria:

  • Prior history of PJI of the same joint treated surgically for infection other than one prior DAIR procedure.
  • Soft tissue defect requiring reconstruction.
  • Hardware misalignment, loosening, or fracture at site of prosthesis that would not allow for retention of prosthesis.
  • Active osteomyelitis or history of osteomyelitis of the same anatomic site not successfully treated as evidenced by one year of follow up.
  • Septic shock or hemodynamic instability.
  • Stage 4 or greater chronic kidney disease, defined as a glomerular filtration rate < 30 mL/min as determined by the Cockcroft-Gault formula or requiring dialysis.
  • Patients with decompensated cirrhosis (e.g., ascites, encephalopathy, or variceal bleeding).
  • History of known alcohol-induced liver disease or non-alcoholic steatohepatitis.
  • Patient with decompensated heart failure.
  • Any other clinically significant disease that in the judgment of the investigator makes the patient unfit for the study or that could jeopardize the safety of the patient or confound the results of the study.
  • Abnormal hematological and biochemical parameters at screening, including:
    • Absolute neutrophil count < 1000 cells/mm^3; or
    • Platelet count < 50,000/mm^3; or
    • Aspartate aminotransferase or alanine aminotransferase value >3×upper limit of normal (ULN).
  • Have a known history of, or positive test result at screening for human immunodeficiency virus (HIV)-1 and HIV-2 antibodies, hepatitis B virus, or hepatitis C virus.
  • Positive test result on the urine drug screen for cocaine, methadone, barbiturates, amphetamine, benzodiazepines, cannabinoids, opiates, or phencyclidine, unless the patient has a medical need for a prescription medication that produces the positive result.
  • Current alcohol or substance abuse that, in the opinion of the investigator, may interfere with the patient’s compliance.
  • Currently receiving chemotherapy, immunosuppressants (greater than 10 mg prednisone per day) or immune modulators.
  • Immunocompromised at screening in the judgment of the investigator, including taking any medication (such as biological response modifiers, active immunomodulating treatment for cancer, or systemic steroids) that causes immunosuppression in the judgment of the investigator, within 1 month prior to the start of screening.
  • Treatment with any antiviral medication within 2 weeks prior to randomization.
  • Participating in another clinical trial (involving experimental intervention), and/or participated in an alternative PJI investigational protocol/study within 1 year prior to screening.
  • Known allergy to phage products or to any ingredient in the phage preparation.
  • Inability to comply with IA or IV phage therapy administration.
  • Pregnant and/or breastfeeding.
  • Lack of capacity to provide informed consent or adhere to the protocol in the judgment of the investigator.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Gina Suh, M.D.

Contact us for the latest status

Contact information:

Hans-Abram Voges

(507) 422-0275

Voges.Hans-Abram@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

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Supplemental Study Information

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