Phase 2
N=114
Repertaxin in Prevention of Primary Graft Dysfunction After Lung Transplantation
Ischemia-Reperfusion Injury · Lung Transplantation
Bottom Line
View on ClinicalTrials.gov: NCT00224406 ↗Enrolled (actual)
114
Serious AEs
27.7%
Results posted
Dec 2024
Primary outcome: Primary: PaO2/FiO2 Ratio at ICU Admission (Time 0) and 24 Hours — 346.3; 337.9; 320.1; 307.3 ratio of PaO2/FiO2 — p=0.8541
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Repertaxin (Drug); Placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Dompé Farmaceutici S.p.A
- Primary completion
- Sep 2006
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY PaO2/FiO2 Ratio at ICU Admission (Time 0) and 24 Hours |
346.3; 337.9; 320.1; 307.3 | 0.8541 |
| SECONDARY PaO2/FiO2 Ratio (ICU Admission Then 24 Hours up to Extubation or up to 72 Hours) |
346.3; 337.9; 320.1; 307.3; 266.1; 279.2 | 0.8654 |
| SECONDARY Number of Patients With Different Primary Graft Dysfunction (PGD) Scores (0-3, and Missing Data) |
0; 1; 28; 33; 9; 8 | 0.7985 |
| SECONDARY Time to Freedom From Mechanical Ventilation |
0.5000; 0.4909; 0.6957; 0.7273; 0.7391; 0.8052 | 0.7076 |
| SECONDARY Probability of Death During Intensive Care Unit (ICU) Stay at Different Timepoints |
0.0000; 0.0364; 0.3261; 0.2909; 0.4783; 0.4962 | 0.9632 |
| SECONDARY Number of Patients Dead Within 30 Days Post-transplant |
0; 1 | — |
| SECONDARY Pulmonary Function Tests (FEV1=Forced Expiratory Volume in One Second and FVC=Forced Vital Capacity) at Month 1, 6 and 12 Post-transplant Evaluated According to Estenne et al.(2002). |
2.20; 2.05; 2.62; 2.34; 2.52; 2.22 | — |
| SECONDARY Number of Patients With Different Bronchiolitis Obliterans Syndrome (BOS) Scores (0-3) Assessed at Months 6 and 12 Post-transplant |
0; 4; 45; 44; 1; 3 | — |
| SECONDARY Number of Patients With at Least One Acute Rejection Episode at Months 1, 6 and 12 Post-transplant |
17; 19; 35; 33; 17; 13 | — |
| SECONDARY Patient Survival up to 12 Months Post-transplant |
0; 3; 0; 5; 0; 6 | 0.0111 sig |
| SECONDARY Number of Patients With at Least One Adverse Events Within the First Month |
46; 55; 1; 0; 14; 14 | — |
| SECONDARY Number of Patients With at Least One Adverse Events From Month 1 to Month 12 |
46; 40; 21; 20; 0; 0 | — |
Summary
The objective of this clinical study was to evaluate whether CXCL8 (CXC ligand 8 [formerly interleukin (IL)-8]) inhibition with repertaxin leads to reduced severity of primary graft dysfunction, as the result of improved functional and clinical outcomes in lung transplantation patients.
The safety of repertaxin in the specific clinical setting was also evaluated.
The ability of repertaxin to reduce target cells (polymorphonuclear leukocyte [PMN]) infiltration into the graft was evaluated to confirm its mechanism of action.
Eligibility Criteria
Inclusion Criteria
- Patients accepted and listed for transplantation due to irreversible, progressive disabling, end-stage pulmonary disease;
- Ages 18 to 65 years;
- Body weight 30 to 95 kg (inclusive) (i.e. up to 95.99 kg);
- Planned isolated (single and bi-lateral) lung transplant from a non-living donor with brain death. This included lobar lung transplant involving excision and sizing of a cadaver donor lobe to meet the thoracic dimension of the recipient before being transplanted;
- Normal renal function at the time of transplant as per calculated creatinine clearance (Clcr) 60 mL/min. Creatinine clearance was calculated according to the Cockcroft-Gault formula;
- Patient was willing and able to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations;
- Patient gave written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent could be withdrawn by the patient at any time without prejudice to their future medical care.
Exclusion Criteria
- Recipients of an intended multiple organ transplant, including heart-lung and liver-lung transplantation;
- Recipients of a lung from a living lobar donor;
- Recipients of a lung from a non-heart beating donor;
- Re-do lung transplantation;
- Recipients requiring mechanical ventilation at the time of transplant;
- Recipients with an extra-respiratory tract site of infection (positive blood culture(s) and/or fever associated with other signs of systemic sepsis syndrome). The criterion was not meant to exclude bacteraemic cystic fibrosis patients with or without fever, unless they presented with other signs of sepsis;
- Recipients with hepatic dysfunction (bilirubin exceeding 3 mg/dL and/or transaminases >3X upper limit of normal [ULN]) at the time of transplant;
- Hypersensitivity to:
- Ibuprofen or to more than one non steroidal anti-inflammatory drug (NSAID);
- Medications belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib;
- Patients simultaneously participating in any other studies involving a study drug to be administered concomitantly with the investigational product and/or a study drug intended to prevent ischemia/reperfusion injury;
- Planned use of anli-CD3 monoclonal antibody (Orthoclone OKT3) or alemtuzumab (Campath) induction immunosuppression;
- Planned use of sirolimus in the first 3 months after transplantation;
- Pregnant or breast-feeding women (NB: pregnancy was lo be avoided in patients or partners during the first month of participation in the study; no other specific warnings were described, considering even stricter general recommendations concerning pregnancy in transplanted patients, the treatment course of the investigational product, its pharmacokinetic profile, and the lack of significant adverse effects on mating performance and fertility in animal studies).
Data sourced from ClinicalTrials.gov (NCT00224406). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.