Study to Test the Validity of the Treatment of Idiopathic Pulmonary Fibrosis With Cotrimoxazole (TriSulfa-FPI)

• ClinicalTrials.gov Identifier: NCT01777737
• Recruitment Status: Terminated
• First Posted: January 29, 2013
• Last Update Posted: November 14, 2017
• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Collaborator: Junta de Andalucia
• Information provided by (Responsible Party): Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Study Description

Brief Summary:

First study to test the validity of the treatment of idiopathic pulmonary fibrosis, which causes inflammation and fibrosis (scarring) of the lung tissue, with cotrimoxazole.

Cotrimoxazole may improve the clinical course of the disease through eradication of Pneumocystis jiroveci colonization and other mechanisms as inhibiting the activation of alveolar macrophages and producing alterations in the surfactant system which favours the persistent activation of the inflammatory response and the development of pulmonary fibrosis.

Condition or disease	Intervention/treatment	Phase
Idiopathic Pulmonary Fibrosis	Drug: Cotrimoxazole; Drug: Placebo	Phase 3

Detailed Description:

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that is clinically manifested by the appearance of effort dyspnea and impaired lung function.

The natural history of the disease is poorly understood and there is no clear consensus as to the most appropriate markers for predicting patient outcome.

This pilot controlled trial aims to test the efficacy and safety of cotrimoxazole in the treatment of IPF. This novel therapeutic strategy, with very encouraging preliminary data is based on its pathophysiological basis, primarily related to the elimination of Pneumocystis colonization. That elimination, could serve as a potent weapon for reducing morbidity and mortality and the cost associated with this devastating disease.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Pilot Study Phase III to Evaluate the Efficacy and Safety of Trimethoprim-sulfamethoxazole in the Treatment of Idiopathic Pulmonary Fibrosis
• Actual Study Start Date: November 25, 2013
• Actual Primary Completion Date: November 5, 2015
• Actual Study Completion Date: November 5, 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cotrimoxazole; Sulfamethoxazole 400 mg. + trimethoprim 80 mg. weight-adjusted	Drug: Cotrimoxazole; 24 weeks of treatment
Placebo Comparator: Placebo; Identical capsules to cotrimoxazole	Drug: Placebo; Identical capsules to cotrimoxazole; Other Name: Placebo with identical physical appearance

Outcome Measures

Primary Outcome Measures :

1. Evaluate the efficacy of oral cotrimoxazole versus placebo in idiopathic pulmonary fibrosis (IPF). [ Time Frame: 24 weeks ]
   Decline of the FVC ≥ 5% at 24 weeks and / or hospitalization for respiratory causes.

Secondary Outcome Measures :

1. Evaluate the safety of oral cotrimoxazole versus placebo in IPF. [ Time Frame: At 24 weeks ]
   • Time to progression
   • Any cause of hospitalization
   • Overall mortality
   • Incidence and severity of adverse events.
2. Evaluate the effect of cotrimoxazole on the natural history of Pneumocystis colonization in patients with IPF. [ Time Frame: 24 weeks ]
   - Molecular diagnosis of colonization by Pneumocystis jiroveci.
3. Identify the effects of cotrimoxazole systemic level of inflammatory activity in patients with IPF. [ Time Frame: At 24 weeks ]
   • Acute exacerbation of IPF
   • Scales of dyspnea
   • Reduction > 50% in the values of different proinflammatory cytokines
   • Reduction > 50% in the values of surfactant proteins.
   • Reduction > 50% in the values of chemokine CCL-18.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patient, regardless of gender, aged 18 to 80 years.
• Well-established diagnostic criteria of the Idiopathic Pulmonary Fibrosis (IPF) as ATA/ERS/JRS/ALAT 2011.
• Ability to obtain a sample of sputum or oropharyngeal washing.
• Forced Vital Capacity (FVC) above 50% from the theoretical value expected.
• Patient compliance or legal guardian to participate in this study by signing the informed consent.

Exclusion Criteria:

• Allergy / hypersensitivity or known gastrointestinal intolerance to cotrimoxazole.
• Use of immunosuppressants or corticosteroids in the previous 90 days at baseline.
• Exacerbation of IPF and / or pneumonia in the 90 days prior to baseline.
• Presence of autoimmune diseases or asthma.
• Patients with other significant diseases other than IPF. It is considered significant disease any disease or condition that, in the investigator's opinion, may jeopardize the patient's health participating in the study or influence the results of the study or the patient's ability to participate in the study.
• Pregnant or lactating or of childbearing potential not using medically approved contraceptive methods at least three months before or during trial.
• Participation in another trial with an investigational drug within 30 days or six half-lives (the larger of the two) above the baseline.

Contacts and Locations

Locations

Spain

Hospital Universitario Virgen del Rocío/ Instituto de Biomedicina de Sevilla

Sevilla, Spain, 41013

Sponsors and Collaborators

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Junta de Andalucia

More Information

• Responsible Party: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• ClinicalTrials.gov Identifier: NCT01777737
• Other Study ID Numbers: TriSulfa-FPI-1
• First Posted: January 29, 2013
• Last Update Posted: November 14, 2017
• Last Verified: November 2017

Keywords provided by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla:

Idiopathic Pulmonary Fibrosis; Trimethoprim-sulfamethoxazole; Pneumocystis jiroveci

Additional relevant MeSH terms:

Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis; Pathologic Processes; Lung Diseases; Respiratory Tract Diseases; Trimethoprim, Sulfamethoxazole Drug Combination; Anti-Infective Agents, Urinary; Anti-Infective Agents; Renal Agents; Anti-Bacterial Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents