Pentoxifylline as an Adjunct Therapy for Patients With Eisenmenger Syndrome

Study Purpose

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	10 Years - 80 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Eisenmenger syndrome in functional class II, III or IV (World Health Organization for Pulmonary Hypertension). 2. Using or not oral anticoagulation with warfarin.

Exclusion Criteria:

1. Hospitalized. 2. History of relevant and/or repetitive bleeding. 3. Relevant comorbidities with specific treatments. 4. Systemic syndromes, except Down syndrome. 5. Candidates for surgical treatment of any nature, except dental. 6. Clinically manifest systemic infectious or inflammatory disease. 7. Thrombocytopenia (<80x10*9 platelets/L). 8. Patients in chronic anticoagulation regimen other than warfarin. 9. Diabetics individuals. 10. Pregnancy in progress, interruption of contraception or amenorrhea. 11. History of intolerance of pentoxifylline or other xanthine derivatives. 12. "Creatinine clearance" less than or equal to 30 mL/minute.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05611268
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	N/A
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University of Sao Paulo General Hospital
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Antonio Augusto Barbosa Lopes, MD
Principal Investigator Affiliation	InCor Heart Institute
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Brazil
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Eisenmenger Syndrome

Additional Details

The Eisenmenger syndrome corresponds to the most advanced form of pulmonary arterial hypertension associated with congenital heart disease. The syndrome causes chronic hypoxemia, with an increase in erythrocyte mass, which predisposes to thrombotic complications. It also involves endothelial dysfunction characterized by increase in the circulating levels of von Willebrand factor, tissue-type plasminogen activator and P-selectin, with a reduction in the plasma concentration of thrombomodulin. The usual drug treatment is represented by the use of prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors and, eventually, anticoagulation with warfarin. However, the difficulty of controlling the chronic use of warfarin and the few studies with other oral anticoagulants, brings the possibility of using drugs not specifically designated as coagulation inhibitors, such as pentoxifylline. This drug is a xanthine derivative and it is considered as a hemorrheological agent with described effects of reduction in erythrocyte and platelet aggregation, adhesion and activation of leukocytes, and endothelial damage. It is, therefore, considered as an agent capable of reducing blood viscosity and improving erythrocyte deformability probably due to an increase in intracellular adenosine triphosphate (ATP), with a reduction in Ca++ and phosphorylation of membrane proteins. The objective of this study is to verify if the chronic oral administration of pentoxifylline: 1) induces an increase in the circulating levels of thrombomodulin, a naturally occurring proteoglycan with anticoagulant, anti thrombotic and anti-inflammatory properties; 2) stabilizes or induces a reduction in circulating tissue factor and thrombin-antithrombin complexes; 3) changes the expression of thrombomodulin and tissue factor in circulating monocytes; 4) offers protection against the occurrence of predefined clinical events; 5) provides improvement in physical capacity, peripheral oxygen saturation, hematocrit level and right ventricular function. The main study outcome is biochemical: change from baseline (increase) in circulating levels of thrombomodulin at 3 months and 6 months of oral use of pentoxifylline. It will be a prospective, single-center, randomized study. Forty-eight adult patients with Eisenmenger syndrome who are already using specific therapies for pulmonary arterial hypertension will be included and these will be randomized to receive pentoxifylline as an adjunctive treatment or remain under routine therapeutic measures for pulmonary arterial hypertension. Oral pentoxifylline will be started at the dose of 400 mg/day for 30 days, followed by 800 mg/day for 5 months, completing the 6-month period of the study. The routine treatment for pulmonary arterial hypertension will be maintained for all patients.

Arms & Interventions

Arms

No Intervention: No treatment group

24 patients that will continue receiving routine treatment for PAH

Other: Pentoxifylline

24 patients that will receive pentoxifylline and the routine treatment for PAH

Interventions

Drug: - Pentoxifylline

Oral Pentoxifylline 400 mg/day for 30 days, followed by 800 mg/day for 150 days

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