Reparixin for Acute Respiratory Distress Syndrome

Recruiting at 44 trial locations

Overseen by Moerer Onnen, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Dompé Farmaceutici S.p.A

Must not be taking: Sulfonamides, COX inhibitors

Disqualifiers: Chronic hepatic disease, Renal dysfunction, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Study objectives 1. To characterize the efficacy of reparixin in ameliorating lung injury and systemic inflammation and expediting clinical recovery and liberation from mechanical ventilation in adult patients with moderate to severe ARDS (PaO2/FIO2 ratio ≤ 200). 2. to assess the effect of reparixin on systemic biomarkers linked to a hyper-inflammatory ARDS phenotype. 3. To evaluate the safety of reparixin vs. placebo in patients enrolled in the study.

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.

What evidence supports the effectiveness of the drug Reparixin for treating acute respiratory distress syndrome (ARDS)?

The research does not provide direct evidence supporting the effectiveness of Reparixin for ARDS, but it highlights the importance of targeting specific patient groups and using innovative trial designs to improve outcomes in ARDS treatments. ^{1 2 3 4 5}

How does the drug reparixin differ from other treatments for acute respiratory distress syndrome?

Reparixin is unique because it specifically inhibits the CXCR1 and CXCR2 receptors, which are involved in inflammation, potentially reducing acute lung injury by limiting neutrophil recruitment and vascular permeability. This mechanism is different from other treatments that may not target these specific pathways. ^{6 7 8 9 10}

Research Team

Moerer Onnen, MD

Principal Investigator

Universitaetsmedizin Goettingen

Eligibility Criteria

Adults over 18 with moderate to severe ARDS, mechanically ventilated, and a specific oxygenation criterion. They must have been in the hospital for less than a week and not be likely to die within 24 hours or need extensive life support soon. Women of childbearing age must use contraception.

Inclusion Criteria

I am over 18 years old.

My breathing issues are not just because of heart problems or fluid in my body.

I am either not able to have children, have been in menopause for at least a year, or have a negative pregnancy test.

Exclusion Criteria

My kidney function is severely impaired or I am on dialysis.

I have stomach movement issues due to pancreatitis or surgery, shown by bloating, feeding problems, or large stomach residuals.

Pregnant or lactating women

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomization and Baseline assessments

Participants are randomized to receive either reparixin or placebo and baseline assessments are conducted

1 day

Treatment

Participants receive reparixin or placebo for 14 days, with a possible extension up to 21 days

14-21 days

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, up to 28 days or hospital discharge, and then up to day 60

Up to 60 days

Treatment Details

Interventions

• Matching Placebo (Other)
• Reparixin (CXC Chemokine Receptor Antagonist)

Trial Overview The trial is testing reparixin's effectiveness in improving lung function and reducing inflammation compared to a placebo in adults with ARDS. It also assesses safety and aims to help patients wean off mechanical ventilation sooner.

Participant Groups

Group I: Reparixin + Standard of care Experimental Treatment 1 Intervention

Reparixin tablets 1200 mg TID (2 tablets x 600 mg TID) as add-on to the standard of care (SoC).

Group II: Placebo + Standard of care Placebo Group 1 Intervention

Placebo tablets with the same schedule of reparixin, as add-on to the standard of care (SoC)

Who Is Running the Clinical Trial?

Dompé Farmaceutici S.p.A

Lead Sponsor

Trials

53

Recruited

4,400+

Founded

:[-1880s implied start, exact date not specified],

Findings from Research

Randomized trials in critical care often show no mortality benefit, which may be due to patient variability or ineffective interventions.

Targeting only patients with a favorable physiological response in studies of acute respiratory distress syndrome (ARDS) could improve the chances of finding effective treatments and reduce the risk of exposing patients to potentially harmful interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiologic Responsiveness Should Guide Entry into Randomized Controlled Trials. Goligher, EC., Kavanagh, BP., Rubenfeld, GD., et al.[2020]

The commentary suggests that the study by Hirano et al. on the effects of steroids in patients with acute respiratory distress syndrome (ARDS) should focus solely on existing randomized control trials to ensure the reliability of the findings.

It emphasizes the need to reassess the certainty of evidence regarding the primary outcomes of steroid treatment in ARDS patients, indicating that current conclusions may need further validation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A reassessment about included studies and certainty of evidence on a systematic review and meta-analysis of steroid for patients with acute respiratory distress syndrome. Yoshihiro, S., Taito, S.[2023]

The ARMA trial demonstrated that low tidal volume ventilation significantly reduces mortality and increases ventilator-free days in ARDS patients compared to conventional ventilation, with a mortality rate of 31.0% versus 39.8%.

Methylprednisolone treatment initiated between 7 and 13 days after ARDS onset improves ventilator-free and shock-free days, but starting treatment after two weeks increases the risk of death, highlighting the importance of timing in corticosteroid therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acute respiratory distress syndrome--treatments today and tomorrow]. Kurahashi, K.[2020]

Lung-protective ventilation strategies, such as using a tidal volume of 6 mL per kg of predicted body weight, have significantly reduced mortality rates in patients with acute respiratory distress syndrome (ARDS).

Future clinical trials for ARDS should focus on targeting specific patient subgroups based on severity and biological factors, and explore new treatment approaches like combination therapies and cell-based therapies to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials in acute respiratory distress syndrome: challenges and opportunities. Matthay, MA., McAuley, DF., Ware, LB.[2022]

To enhance the development of new treatments for acute respiratory distress syndrome (ARDS), it is crucial to identify appropriate molecular targets and improve trial methodologies, including realistic sample sizes and meaningful endpoints.

Biomarker-driven studies and the categorization of specific ARDS subsets could help identify at-risk populations that are most likely to benefit from new therapies, suggesting a need for innovative clinical trial designs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial design in prevention and treatment of acute respiratory distress syndrome. Curley, GF., McAuley, DF.[2020]

In a study involving female Wistar rats with spinal cord injury, treatment with 15 mg/kg of Reparixin significantly reduced inflammation markers (TNF-α and CINC-1) and improved motor function and neuron survival in the spinal cord.

Reparixin also effectively decreased the severity of autonomic dysreflexia, a common complication after spinal cord injury, indicating its potential as a therapeutic intervention for managing both inflammation and functional recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of CXCR1 and CXCR2 chemokine receptors attenuates acute inflammation, preserves gray matter and diminishes autonomic dysreflexia after spinal cord injury. Marsh, DR., Flemming, JM.[2021]

Reparixin significantly reduced all-cause mortality in critically ill or transplant patients, with a mortality rate of 3.4% in the reparixin group compared to 6.4% in the control group, based on a meta-analysis of nine studies involving 733 patients.

The use of reparixin did not increase the risk of infections such as pneumonia or sepsis, indicating it is a safe option for improving survival in both COVID-19 and non-COVID-19 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reparixin improves survival in critically ill and transplant patients: A meta-analysis. Piersanti, G., Landoni, G., Scquizzato, T., et al.[2023]

Reparixin, a CXCR2 inhibitor, significantly reduced neutrophil recruitment and vascular permeability in two mouse models of acute lung injury (ALI), demonstrating its potential as a therapeutic intervention.

In both prophylactic and therapeutic applications, Reparixin improved gas exchange and reduced inflammation in ALI, indicating its efficacy in managing this critical condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic inhibition of CXCR2 by Reparixin attenuates acute lung injury in mice. Zarbock, A., Allegretti, M., Ley, K.[2022]

In a meta-analysis of six randomized controlled trials involving 406 patients, reparixin significantly reduced all-cause mortality in high-risk patients, with only 2.3% mortality in the reparixin group compared to 6.5% in the control group.

Reparixin's use did not increase the risk of pneumonia, sepsis, or non-serious infections, indicating it is a safe option for improving survival in critically ill patients without compromising their infection risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of reparixin on survival in patients at high risk for in-hospital mortality: a meta-analysis of randomized trials. Landoni, G., Zangrillo, A., Piersanti, G., et al.[2022]

References

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

Physiologic Responsiveness Should Guide Entry into Randomized Controlled Trials. [2020]

2. England pubmed.ncbi.nlm.nih.gov

A reassessment about included studies and certainty of evidence on a systematic review and meta-analysis of steroid for patients with acute respiratory distress syndrome. [2023]

3. Japan pubmed.ncbi.nlm.nih.gov

[Acute respiratory distress syndrome--treatments today and tomorrow]. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Clinical trials in acute respiratory distress syndrome: challenges and opportunities. [2022]

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

Clinical trial design in prevention and treatment of acute respiratory distress syndrome. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Inhibition of CXCR1 and CXCR2 chemokine receptors attenuates acute inflammation, preserves gray matter and diminishes autonomic dysreflexia after spinal cord injury. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Reparixin improves survival in critically ill and transplant patients: A meta-analysis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Reparixin, a specific interleukin-8 inhibitor, has no effects on inflammation during endotoxemia. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Therapeutic inhibition of CXCR2 by Reparixin attenuates acute lung injury in mice. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

The effect of reparixin on survival in patients at high risk for in-hospital mortality: a meta-analysis of randomized trials. [2022]