Last reviewed · How we verify

NCT00224406

Repertaxin in Prevention of Primary Graft Dysfunction After Lung Transplantation

Completed Phase 2 Results posted Last updated 11 December 2024
What this trial tests

Phase 2 trial testing Repertaxin in Ischemia-Reperfusion Injury in 114 participants. Completed in 13 September 2007.

Timeline
1 May 2005
Primary endpoint
13 September 2006
13 September 2007

Quick facts

Lead sponsorDompé Farmaceutici S.p.A
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposeprevention
Enrollment114
Start date1 May 2005
Primary completion13 September 2006
Estimated completion13 September 2007
Sites6 locations across Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

Dompé Farmaceutici S.p.A — full company profile →

Who can join

Adults 18 to 65, any sex, with Ischemia-Reperfusion Injury or Lung Transplantation. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

PaO2/FiO2 Ratio at ICU Admission (Time 0) and 24 Hours Primary · At T0 (time of ICU admission) and 24 hours post-ICU admission

The PaO2/FiO2 ratio was calculated to assess the severity of hypoxemia, or low blood oxygen levels. A low PaO2/FiO2 value has been associated with increased mortality and hospital stay in patients admitted to the intensive care unit (ICU). It was calculated by dividing the partial pressure of oxygen in arterial blood (PaO2) by the fraction of inspired oxygen (FiO2). A normal P/F ratio was typically above 300, and a lower ratio indicates a greater severity of hypoxemia. As the Pa02/Fi02 ratio was dependent on altitude, data were corrected for altitude in the analyses of corrected data. The corr

ICU Admission (Time 0)
GroupValue95% CI
Repertaxin (ITT)346.3± 125.5
Placebo (ITT)337.9± 143.0
24 Hours Post ICU Admission
GroupValue95% CI
Repertaxin (ITT)320.1± 119.5
Placebo (ITT)307.3± 111.3
PaO2/FiO2 Ratio (ICU Admission Then 24 Hours up to Extubation or up to 72 Hours) Secondary · At ICU admission (T0), 24, 48 and 72 hours post-ICU admission

Time profile of oxygenation was a comparison of the sequential measurements of the ratios of arterial PaO2 to inspired oxygen fractions FiO2. Herein repeated measurements analysis of PaO2/FiO2 ratio corrected after ICU admission using a one-sided test excluding missing data.

ICU Admission (Time 0)
GroupValue95% CI
Repertaxin (ITT)346.3± 125.5
Placebo (ITT)337.9± 143.0
24 Hours Post ICU Admission
GroupValue95% CI
Repertaxin (ITT)320.1± 119.5
Placebo (ITT)307.3± 111.3
48 Hours Post ICU Admission
GroupValue95% CI
Repertaxin (ITT)266.1± 117.3
Placebo (ITT)279.2± 151.8
72 Hours Post ICU Admission
GroupValue95% CI
Repertaxin (ITT)275.6± 88.1
Placebo (ITT)233.9± 132.0
Number of Patients With Different Primary Graft Dysfunction (PGD) Scores (0-3, and Missing Data) Secondary · At ICU admission (T0), 24, 48 and 72 hours post-ICU admission

PGD after lung transplantation ranged from mild to severe depending on the level of hypoxaemia and lung injury post-transplant. PGD score was calculated according to the scoring system below: Grade 0 PaO2/FiO2 \>=300 mmHg; no radiographic infiltrates (RI); Grade 1 PaO2/FiO2 \>=300mmHg + RI consistent with pulmonary oedema; Grade 2 200 mmHg \<=PaO2/FiO2 \<=300 mm Hg + RI consistent with pulmonary oedema; Grade 3 PaO2/FiO2 \< 200 mm Hg + RI consistent with pulmonary oedema. The higher the score, the worse the outcome. Any patient with no infiltrate on chest X-rays was automatically Grade 0. If

ICU Admission (Time 0) - PGD Score Missing
GroupValue95% CI
Repertaxin (ITT)0
Placebo (ITT)1
ICU Admission (Time 0) - PGD Score 0
GroupValue95% CI
Repertaxin (ITT)28
Placebo (ITT)33
ICU Admission (Time 0) - PGD Score 1
GroupValue95% CI
Repertaxin (ITT)9
Placebo (ITT)8
ICU Admission (Time 0) - PGD Score 2
GroupValue95% CI
Repertaxin (ITT)6
Placebo (ITT)4
ICU Admission (Time 0) - PGD Score 3
GroupValue95% CI
Repertaxin (ITT)3
Placebo (ITT)9
24 Hours Post ICU Admission - PGD Score Missing
GroupValue95% CI
Repertaxin (ITT)0
Placebo (ITT)1
24 Hours Post ICU Admission - PGD Score 0
GroupValue95% CI
Repertaxin (ITT)22
Placebo (ITT)30
24 Hours Post ICU Admission - PGD Score 1
GroupValue95% CI
Repertaxin (ITT)14
Placebo (ITT)12
Time to Freedom From Mechanical Ventilation Secondary · At 24, 48, 72 hours post ICU admission

Time to freedom from mechanical ventilation was defined as "time between admission to the ICU and the initial time of first extubation (breathing off mechanical ventilation without a tube) which was maintained for more than 24 hours". This number was measured in hours and was derived as (date/time of extubation-date/time of ICU admission)/3600. The longer the time, the worst the outcome.Time to freedom from mechanical ventilation, if greater than 1 month (720 hours), was censored to 720 hours. Patients re-transplanted were censored at the date/time of re-transplant. Herein differences in the t

24 Hours Post-ICU Admission
GroupValue95% CI
Repertaxin (ITT)0.5000± 0.0737
Placebo (ITT)0.4909± 0.0674
48 Hours Post-ICU Admission
GroupValue95% CI
Repertaxin (ITT)0.6957± 0.0678
Placebo (ITT)0.7273± 0.0601
72 Hours Post-ICU Admission
GroupValue95% CI
Repertaxin (ITT)0.7391± 0.0647
Placebo (ITT)0.8052± 0.0541
Probability of Death During Intensive Care Unit (ICU) Stay at Different Timepoints Secondary · At 24, 48, 72 hours post ICU admission

The duration of ICU stay, in term of hours, at different timepoints, in both placebo and repertaxin groups, was measured. The longer the ICU stay, the worse the outcome. mean event probability" (death) and its standard error (SE) at each timepoint.

At 24 h hours post ICU admission
GroupValue95% CI
Repertaxin (ITT)0.0000± 0.0000
Placebo (ITT)0.0364± 0.0252
At 48 h hours post ICU admission
GroupValue95% CI
Repertaxin (ITT)0.3261± 0.0691
Placebo (ITT)0.2909± 0.0612
At 72 h hours post ICU admission
GroupValue95% CI
Repertaxin (ITT)0.4783± 0.0737
Placebo (ITT)0.4962± 0.0679
Number of Patients Dead Within 30 Days Post-transplant Secondary · Up to 30 days post-transplant

Mortality, defined as any death occurring in the first 30 days post-transplant, regardless of hospital discharge.

GroupValue95% CI
Repertaxin (ITT)0
Placebo (ITT)1
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). Secondary · At months 1, 6 and 12 post-transplant

Forced expiratory volume in 1 second (FEV1) measured the amount/ volume, exhaled by a patient in the first second of the expiration after a full inspiration. Average values in healthy patients aged 20-60 range from 4.5 to 3.5 liters in males and from 3.25 to 2.5 liters in females. Forced vital capacity (FVC) was the volume of air that a patient could exhale with a maximal forced expiration effort after a deep inhaling, simply put, how much air a patient could breathe out by blowing as fast as possible. Average values in healthy patients aged 20-60 range from 5.5 to 4.75 liters in males and fro

FEV1 - Month 1 post transplant
GroupValue95% CI
Repertaxin (ITT)2.20± 0.74
Placebo (ITT)2.05± 0.84
FEV1 - Month 6 post transplant
GroupValue95% CI
Repertaxin (ITT)2.62± 0.95
Placebo (ITT)2.34± 0.85
FEV1 - Month 12 post transplant
GroupValue95% CI
Repertaxin (ITT)2.52± 1.07
Placebo (ITT)2.22± 0.95
FVC - Month 1 post transplant
GroupValue95% CI
Repertaxin (ITT)2.49± 0.70
Placebo (ITT)2.56± 1.01
FVC - Month 6 post transplant
GroupValue95% CI
Repertaxin (ITT)3.19± 0.93
Placebo (ITT)3.11± 0.99
FVC - Month 12 post transplant
GroupValue95% CI
Repertaxin (ITT)3.19± 1.05
Placebo (ITT)3.07± 1.10
Number of Patients With Different Bronchiolitis Obliterans Syndrome (BOS) Scores (0-3) Assessed at Months 6 and 12 Post-transplant Secondary · At Months 6 and 12 post-transplant

BOS is defined as an irreversible decline in forced expiratory volume in 1 second (FEV1) of at least 20% from baseline. Spirometric measurements must be made with equipment that conforms to the American Thoracic Society standards for spirometric testing. Here the classification where stage 3 is the worst: BOS 0 FEV1 \>90% of baseline and FEF25-75 \>75% of baseline. BOS 0-p FEV1 \>81% to 90% of baseline and/or FEF25-75 \> 75% of baseline. BOS 1 FEV1 \>66% to 80% of baseline. BOS 2 FEV1 \>51% to 65% of baseline BOS 3 FEV1 \>50% or less of baseline. CRF data are reported.

Month 6 Post Transplant - BOS Missing
GroupValue95% CI
Repertaxin (ITT)0
Placebo (ITT)4
Month 6 Post Transplant - BOS 0
GroupValue95% CI
Repertaxin (ITT)45
Placebo (ITT)44
Month 6 Post Transplant - BOS 1
GroupValue95% CI
Repertaxin (ITT)1
Placebo (ITT)3
Month 6 Post Transplant - BOS 2
GroupValue95% CI
Repertaxin (ITT)0
Placebo (ITT)1
Month 6 Post Transplant - BOS 3
GroupValue95% CI
Repertaxin (ITT)0
Placebo (ITT)0
Month 12 Post Transplant - Missing
GroupValue95% CI
Repertaxin (ITT)4
Placebo (ITT)7
Month 12 Post Transplant - BOS 0
GroupValue95% CI
Repertaxin (ITT)35
Placebo (ITT)36
Month 12 Post Transplant - BOS 1
GroupValue95% CI
Repertaxin (ITT)1
Placebo (ITT)5
Number of Patients With at Least One Acute Rejection Episode at Months 1, 6 and 12 Post-transplant Secondary · At months 1, 6 and 12 post-transplant

Acute rejection was diagnosed according to Yousem et al. (1996). Histopathologic assessment of transbronchial biopsies first required confirmation of the diagnosis of mild (ACR; A2) using criteria defined in the Working Formulation for Lung Allograft Rejection. Morphological variables assessed included: one or more perivascular infiltrates in the total transbronchial biopsy fragments obtained at one bronchoscopy session, the presence of large or small airway inflammation, endothelialitis, eosinophils, plasma cells, intra-airway and intra-airspace granulation tissue, and alveolar hemosiderosis.

Month 1 Post transplant
GroupValue95% CI
Repertaxin (ITT)17
Placebo (ITT)19
Month 6 Post Transplant
GroupValue95% CI
Repertaxin (ITT)35
Placebo (ITT)33
Month 12 Post Transplant
GroupValue95% CI
Repertaxin (ITT)17
Placebo (ITT)13
Patient Survival up to 12 Months Post-transplant Secondary · at Months 3, 6, 9 and 12 post-transplant

Patient survival is derived from the date of ICU admission untile the date of death or study completion/withdrawal. Here this parameter is expressed as the "cumulative number of events (death)" at different timepoints till month 12, per arm.

3 Months
GroupValue95% CI
Repertaxin (ITT)0
Placebo (ITT)3
6 Months
GroupValue95% CI
Repertaxin (ITT)0
Placebo (ITT)5
9 Months
GroupValue95% CI
Repertaxin (ITT)0
Placebo (ITT)6
12 Months
GroupValue95% CI
Repertaxin (ITT)0
Placebo (ITT)7
Number of Patients With at Least One Adverse Events Within the First Month Secondary · to month 1

An AE was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Number (%) of patients reporting at least one TEAE
GroupValue95% CI
Repertaxin (SAF)46
Placebo (SAF)55
Number (%) of patients reporting at least one TEAE leading to discontinuation of study drug
GroupValue95% CI
Repertaxin (SAF)1
Placebo (SAF)0
Number (%) of patients reporting at least one serious TEAE
GroupValue95% CI
Repertaxin (SAF)14
Placebo (SAF)14
Number (%) of patients reporting at least one TEAE leading to death
GroupValue95% CI
Repertaxin (SAF)0
Placebo (SAF)0
Number (%) of patients reporting TEAEs with no relationship to study drug
GroupValue95% CI
Repertaxin (SAF)19
Placebo (SAF)26
Number (%) of patients reporting TEAEs with unlikely relationship to study drug
GroupValue95% CI
Repertaxin (SAF)18
Placebo (SAF)22
Number (%) of patients reporting TEAEs with possible study drug
GroupValue95% CI
Repertaxin (SAF)9
Placebo (SAF)7
Number (%) of patients reporting TEAEs with probable relationship to study drug
GroupValue95% CI
Repertaxin (SAF)0
Placebo (SAF)0
Number of Patients With at Least One Adverse Events From Month 1 to Month 12 Secondary · from month 1 to month 12

An AE was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Number of patients with TEAEs
GroupValue95% CI
Repertaxin (SAF)46
Placebo (SAF)40
Number (%) of patients reporting at least one TEAE
GroupValue95% CI
Repertaxin (SAF)21
Placebo (SAF)20
Number (%) of patients reporting at least one TEAE leading to discontinuation of study drug
GroupValue95% CI
Repertaxin (SAF)0
Placebo (SAF)0
Number (%) of patients reporting at least one serious TEAE
GroupValue95% CI
Repertaxin (SAF)0
Placebo (SAF)0
Number (%) of patients reporting at least one TEAE leading to death
GroupValue95% CI
Repertaxin (SAF)0
Placebo (SAF)0
Number (%) of patients reporting TEAEs with no relationship to study drug
GroupValue95% CI
Repertaxin (SAF)11
Placebo (SAF)9
Number (%) of patients reporting TEAEs with unlikely relationship to study drug
GroupValue95% CI
Repertaxin (SAF)9
Placebo (SAF)8
Number (%) of patients reporting TEAEs with possible relationship to study drug
GroupValue95% CI
Repertaxin (SAF)1
Placebo (SAF)3

Adverse events — posted to ClinicalTrials.gov

Time frame: The specific period of time over which adverse events data were collected was from the start of infusion to Month 12 visit. Note that in Placebo population the number of subject was 52 instead of 55 in the period from Month 1 to Month 12.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Repertaxin (SAF)
Serious: 14/46 (30%)
Deaths: 1/46
Placebo (SAF)
Serious: 14/55 (25%)
Deaths: 6/55

Serious adverse events (30 terms)

ReactionSystemRepertaxin (SAF)Placebo (SAF)
CoagulopathyBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
HaemorrageVascular disorders
HypotensionVascular disorders
Lung transplant rejectionImmune system disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Pulmonary oedemaRespiratory, thoracic and mediastinal disorders
Reperfusion injuryVascular disorders
ThrombocytopeniaBlood and lymphatic system disorders
Atrial flutterCardiac disorders
Cardiac arrestCardiac disorders
Cardiac tamponadeCardiac disorders
Cardiopulmonary failureCardiac disorders
PericarditisCardiac disorders
Supraventricular TachycardiaCardiac disorders
Cytokine release SyndromeImmune system disorders
PneumoniaInfections and infestations
Graft dysfunctionInjury, poisoning and procedural complications
Post procedural haemorrhageInjury, poisoning and procedural complications
Oxygen saturation decreasedInvestigations
Depressed level of consciousnessNervous system disorders
HemiparesisNervous system disorders
Vocal cord paralysisNervous system disorders
Renal failureRenal and urinary disorders
Other adverse events (204 terms — click to expand)

ReactionSystemRepertaxin (SAF)Placebo (SAF)
Incision site complicationInjury, poisoning and procedural complications
ConstipationGastrointestinal disorders
HyperglycaemiaMetabolism and nutrition disorders
NauseaGastrointestinal disorders
HypomagnesaemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
HypervolaemiaMetabolism and nutrition disorders
HypotensionVascular disorders
AnaemiaBlood and lymphatic system disorders
HypophosphataemiaMetabolism and nutrition disorders
HypovolaemiaMetabolism and nutrition disorders
HypocalcaemiaMetabolism and nutrition disorders
InsomniaPsychiatric disorders
PainGeneral disorders
HaemorrhageVascular disorders
Atrial fibrillationCardiac disorders
TachycardiaCardiac disorders
PyrexiaGeneral disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
Pulmonary oedemaRespiratory, thoracic and mediastinal disorders
Chest painGeneral disorders
OedemaGeneral disorders
AnxietyPsychiatric disorders
PneumoniaInfections and infestations
Back painMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
Oedema peripheralGeneral disorders
Liver function test abnormalInvestigations
White blood cell count increasedInvestigations
HyperkalaemiaMetabolism and nutrition disorders
Shoulder painMusculoskeletal and connective tissue disorders
Crackles lungRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
CoagulopathyBlood and lymphatic system disorders
ThromobocytopeniaBlood and lymphatic system disorders
Supraventricular tachycardiaCardiac disorders

Most-reported serious reactions: Coagulopathy, Atrial fibrillation, Pneumothorax, Haemorrage, Hypotension, Lung transplant rejection, Respiratory failure, Pulmonary oedema.

Data from ClinicalTrials.gov NCT00224406 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The CXCL8-CXCR1/2 pathways in cancer.
    Liu Q, Li A, Tian Y, Wu JD, et al · · 2016 · cited 512× · PMID 27578214 · DOI 10.1016/j.cytogfr.2016.08.002
  2. The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.
    Cambier S, Gouwy M, Proost P. · · 2023 · cited 387× · PMID 36725964 · DOI 10.1038/s41423-023-00974-6
  3. Multiple Roles for Chemokines in Neutrophil Biology.
    Capucetti A, Albano F, Bonecchi R. · · 2020 · cited 230× · PMID 32733442 · DOI 10.3389/fimmu.2020.01259
  4. Circulating IL-6 mediates lung injury via CXCL1 production after acute kidney injury in mice.
    Ahuja N, Andres-Hernando A, Altmann C, Bhargava R, et al · · 2012 · cited 101× · PMID 22791336 · DOI 10.1152/ajprenal.00025.2012
  5. Wound healing and cancer stem cells: inflammation as a driver of treatment resistance in breast cancer.
    Arnold KM, Opdenaker LM, Flynn D, Sims-Mourtada J. · · 2015 · cited 84× · PMID 25674014 · DOI 10.4137/cgm.s11286
  6. Therapeutic inhibition of CXCR1/2: where do we stand?
    Sitaru S, Budke A, Bertini R, Sperandio M. · · 2023 · cited 40× · PMID 37249756 · DOI 10.1007/s11739-023-03309-5
  7. Significance of the IL-8 pathway for immunotherapy.
    Gonzalez-Aparicio M, Alfaro C. · · 2020 · cited 37× · PMID 31860375 · DOI 10.1080/21645515.2019.1696075
  8. Multifaceted Roles of Chemokine C-X-C Motif Ligand 7 in Inflammatory Diseases and Cancer.
    Wu Q, Tu H, Li J. · · 2022 · cited 25× · PMID 35837284 · DOI 10.3389/fphar.2022.914730

Verify or expand the search:

Other recruiting trials for Ischemia-Reperfusion Injury

Currently open trials in the same condition.

Other Dompé Farmaceutici S.p.A trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00224406.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing