Reparixin for Acute Respiratory Distress Syndrome

No longer recruiting at 46 trial locations

Overseen By Enrico Minnella, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dompé Farmaceutici S.p.A

Must not be taking: Sulfonamides, COX inhibitors

Disqualifiers: Chronic hepatic disease, Renal dysfunction, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 14-21 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if reparixin can benefit individuals with moderate to severe acute respiratory distress syndrome (ARDS), a serious lung condition that makes breathing difficult. Researchers seek to discover if reparixin can reduce lung damage, lower inflammation, and expedite recovery from ventilator use. Participants will receive either reparixin or a placebo, alongside standard care, to compare outcomes. Suitable candidates have ARDS with breathing difficulties not caused by heart problems and have recently been on a ventilator. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that reparixin is likely to be safe for humans?

Research has shown that reparixin is generally safe for people. In other studies involving patients with severe breathing problems, reparixin was well-tolerated. For instance, one study found that a similar number of patients in both the reparixin and placebo groups survived without major complications. This suggests that reparixin does not cause more serious issues than a placebo.

While these studies are encouraging, it's important to remember that the current trial is in an early stage. Researchers are still learning about its safety and effectiveness for treating acute respiratory distress syndrome (ARDS). However, past study results suggest that reparixin could be a safe option to explore further. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ARDS?

Unlike the standard of care for Acute Respiratory Distress Syndrome, which typically includes supportive treatments like mechanical ventilation and corticosteroids, Reparixin offers a novel approach. Reparixin is unique because it targets the CXCR1 and CXCR2 chemokine receptors, which play a role in inflammation and immune response. This mechanism could potentially reduce the inflammatory damage in the lungs more effectively than current treatments. Researchers are excited about Reparixin because it has the potential to improve outcomes by specifically addressing the underlying inflammatory process in ARDS, rather than just managing symptoms.

What evidence suggests that reparixin might be an effective treatment for ARDS?

Research has shown that reparixin might help people with acute respiratory distress syndrome (ARDS). In earlier studies, patients with severe COVID-19 experienced better health outcomes after taking reparixin, including improved lung function and reduced inflammation. In this trial, some participants will receive reparixin as an add-on to the standard of care, while others will receive a placebo on the same schedule. The treatment blocks specific parts of the body that cause inflammation. Early results suggest that reparixin can help people recover faster and reduce the need for breathing machines. Overall, promising evidence indicates that reparixin could benefit those with ARDS. ^{2 6 7 8 9}

Who Is on the Research Team?

Moerer Onnen, MD

Principal Investigator

Universitaetsmedizin Goettingen

Are You a Good Fit for This Trial?

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

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.

My chest X-ray or CT scan shows signs of fluid in my lungs.

Exclusion Criteria

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

Pregnant or lactating women

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Matching Placebo
• Reparixin

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.

How Is the Trial Designed?

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],

Published Research Related to This Trial

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 was found to be safe in a study involving 20 healthy male volunteers, but it did not significantly affect neutrophilia or other markers of systemic inflammation induced by endotoxin.

Despite its ability to suppress thromboxane B2 levels, reparixin did not alter the release of pro-inflammatory cytokines like TNF-alpha or IL-6, indicating it does not enhance inflammation in this model, unlike its metabolite ibuprofen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reparixin, a specific interleukin-8 inhibitor, has no effects on inflammation during endotoxemia. Leitner, JM., Mayr, FB., Firbas, C., et al.[2021]

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]

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]

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]

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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35618953/

A Multicenter Phase 2 Randomized Controlled Study on ... Reparixin treatment appeared to be well tolerated. Conclusion: In patients with severe COVID-19, reparixin led to an improvement in clinical outcomes when ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05496868

Add-on Reparixin in Adult Patients With ARDS Study Overview. To characterize the efficacy of reparixin in ameliorating lung injury and systemic inflammation and expediting clinical recovery and liberation ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9135383/

A Multicenter Phase 2 Randomized Controlled Study on the ... The aim of this clinical trial was to determine if CXCR1/2 blockade with reparixin can improve clinical outcomes in hospitalized patients with severe COVID-19 ...

4. withpower.com withpower.com/trial/phase-2-respiratory-distress-syndrome-8-2022-95761

Reparixin for Acute Respiratory Distress Syndrome Trial Overview The trial is testing reparixin's effectiveness in improving lung function and reducing inflammation compared to a placebo in adults with ARDS.

5. dompe.com dompe.com/us/media/press-releases/dompe-announces-results-of-phase-2-study-evaluating-the-efficacy-and-safety-of-reparixin-in-patients-with-severe-covid-19-pneumonia/

Dompé Announces Results of Phase 2 Study Evaluating ... Dompé today announced results from its Phase 2 clinical trial demonstrating that, in patients in severe COVID-19 Pneumonia, Reparixin led to an improvement in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05496868

Add-on Reparixin in Adult Patients With ARDS Study objectives. To characterize the efficacy of reparixin in ameliorating lung injury and systemic inflammation and expediting clinical recovery and ...

7. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-reparixin-for-adults-with-acute-respiratory-distress-syndrome/

Study on the Effectiveness and Safety of Reparixin ... This study investigates the effectiveness and safety of Reparixin, a potential treatment for adults suffering from Acute Respiratory ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10600076/

Efficacy and Safety of Reparixin in Patients with Severe ... For the key secondary outcomes (Table 2), 141 patients (88.7%) in the reparixin group and 66 (84.6%) in the placebo group were alive and free of ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04878055?cond=Pneumonia,%20Viral&rank=5

Study on Efficacy and Safety of Reparixin in the Treatment ... This is a phase 3 clinical trial designed as a randomized, double-blind, placebo-controlled, multicentre study to evaluate the efficacy and safety of ...