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

Pilot Study Phase III to Evaluate the Efficacy and Safety of Trimethoprim-sulfamethoxazole in the Treatment of Idiopathic Pulmonary Fibrosis

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.

Study Overview

• Status: Terminated
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Cotrimoxazole; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocío/ Instituto de Biomedicina de Sevilla

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: Placebo with identical physical appearance

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the safety of oral cotrimoxazole versus placebo in IPF.	Time to progression; Any cause of hospitalization; Overall mortality; Incidence and severity of adverse events.	At 24 weeks
Evaluate the effect of cotrimoxazole on the natural history of Pneumocystis colonization in patients with IPF.	- Molecular diagnosis of colonization by Pneumocystis jiroveci.	24 weeks
Identify the effects of cotrimoxazole systemic level of inflammatory activity in patients with IPF.	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.	At 24 weeks

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Collaborators: Junta de Andalucia

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2013
• Primary Completion (Actual): November 5, 2015
• Study Completion (Actual): November 5, 2015

Study Registration Dates

• First Submitted: January 25, 2013
• First Submitted That Met QC Criteria: January 28, 2013
• First Posted (Estimate): January 29, 2013

Study Record Updates

• Last Update Posted (Actual): November 14, 2017
• Last Update Submitted That Met QC Criteria: November 13, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Idiopathic Pulmonary Fibrosis; Trimethoprim-sulfamethoxazole; Pneumocystis jiroveci
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anti-Infective Agents, Urinary; Renal Agents; Trimethoprim, Sulfamethoxazole Drug Combination
• Other Study ID Numbers: TriSulfa-FPI-1