A Phase 2/3 interventional study of Sildenafil and Losartan in Idiopathic Pulmonary Fibrosis and Pulmonary Fibrosis, sponsored by Alicia Gerke. Terminated at 1 site in United States. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2018-11-13.
Sponsored by Alicia Gerke · Phase 2/3, Interventional, and Treatment
The purpose of this study is to determine whether combination therapy with sildenafil and losartan can improve function and exercise tolerance in patients with idiopathic pulmonary fibrosis.
It is currently suspected that the fibrosis in IPF is based upon an abnormal reparative process in the lung. Normally, an insult to the endothelium or epithelium of the lung would trigger an inflammatory process to help repair the site of injury; epithelial and endothelial cells then replicate and repair the tissue damage. In pulmonary fibrosis, alterations in this cascade change the balance of the inflammatory products and reduce the regulatory response which can produce continued inflammation. Fibrosis results from continued deposition of collagen by proliferating fibroblasts and lack of collagen breakdown.
In addition to fibrosis and microvascular destruction, pulmonary hypertension in IPF patients is a significant contributor to morbidity and mortality. The prevalence ranges from 32-85%, suggesting that pulmonary vascular disease is one of several processes that contribute to severity of disease.
We propose use of two therapeutic agents that affect the balance of vasoconstriction and vasodilation to improve basal tone of the vasculature. First, we propose the use of a phosphodiesterase inhibitor. Sildenafil (Viagra, Revatio) is an orally administered vasodilator that prolongs the effect of nitric oxide by inhibiting phosphodiesterase type 5 (PDE-5) which is responsible for degradation of cGMP. Increased cGMP concentration results in pulmonary vasculature relaxation and consequent vasodilation. Second, the use of an angiotensin receptor blocker (ARB) acts to diminish the direct vasoconstrictor effect of angiotensin and endothelin-1 in the vessels. In treatment of systemic hypertension, ARBs have been shown to be associated with a decrease in the amount of circulating endothelin-1 and increase in basal nitric oxide release. They have also been shown to rapidly inhibit the generation of reactive oxygen species by inflammatory cells. We test these interventions in a randomized cross-over trial in IPF patients.
680 studies on the registry are indexed under Pulmonary Fibrosis; 119 are open to participants now.
This study's enrollment of 12 is below the median of 50 across 419 interventional studies indexed under Pulmonary Fibrosis.
Browse Pulmonary Fibrosis studies →Alicia Gerke is the lead sponsor of 2 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Study participants are patients that have been diagnosed with idiopathic pulmonary fibrosis (IPF).
Drug: Sildenafil · Drug: Losartan · Drug: Sildenafil and Losartan · Drug: Placebo Oral Tablet
Sildenafil 20mg three times per day for 3 months followed by a one month washout prior to next intervention.
Also known as: Viagra, Revatio
Losartan 25mg two times a day for 3 months followed by a one month washout prior to next intervention.
Also known as: Cozaar: losartan
Sildenafil 20mg three times per day and Losartan 25mg two times per day followed by a one month washout prior to next intervention.
Also known as: Viagra, Revatio: sildenafil, Cozaar: losartan
Placebo pill three times per day for 3 months followed by a one month washout prior to next intervention.
Also known as: Placebo pill (sugar)
Change in Six Minute Walk Distance in Meters
Change in 6MWD before and after treatment compared to placebo
Time frame: At baseline and three months post each intervention.
Change in Forced Vital Capacity (FVC)
Change in FVC before and after treatment compared to placebo. FVC is a measure of lung size.
Time frame: At baseline and three months post each intervention.
Change in Shortness of Breath (SOB) Score
Change in symptoms of SOB as determined by St. Georges Respiratory Questionnaire score. This score ranges from 0 to 100 with a higher score indicating more problems breathing.
Time frame: At baseline and three months post each intervention.
| Milestone | All Study Participants |
|---|---|
| Started | 12 |
| Started losartan | 12 |
| Completed losartan | 10 |
| Completed | 10 |
| Not completed | 2 |
| Withdrew: Withdrawal by subject | 1 |
| Withdrew: Death | 1 |
| Milestone | All Study Participants |
|---|---|
| Started | 10 |
| Started placebo oral tablet | 10 |
| Completed placebo oral tablet | 9 |
| Completed | 9 |
| Not completed | 1 |
| Withdrew: Withdrawal by subject | 1 |
| Milestone | All Study Participants |
|---|---|
| Started | 9 |
| Started sildenafil | 9 |
| Completed sildenafil | 9 |
| Completed | 9 |
| Not completed | 0 |
| Milestone | All Study Participants |
|---|---|
| Started | 9 |
| Started sildenafil and losartan | 9 |
| Completed sildenafil and losartan | 9 |
| Completed | 9 |
| Not completed | 0 |
Change in 6MWD before and after treatment compared to placebo
| meters | Sildenafil | Losartan | Sildenafil and Losartan | Placebo |
|---|---|---|---|---|
| Change in Six Minute Walk Distance in Meters | 10.5 ± 23.1 | 15.8 ± 24.0 | -11.1 ± 12.0 | 12.1 ± 23.8 |
Change in FVC before and after treatment compared to placebo. FVC is a measure of lung size.
| liters | Sildenafil | Losartan | Sildenafil and Losartan | Placebo |
|---|---|---|---|---|
| Change in Forced Vital Capacity (FVC) | -0.04 ± .13 | -0.06 ± 0.13 | 0.002 ± 0.14 | -0.02 ± 0.14 |
Change in symptoms of SOB as determined by St. Georges Respiratory Questionnaire score. This score ranges from 0 to 100 with a higher score indicating more problems breathing.
| score on a scale | Sildenafil | Losartan | Sildenafil and Losartan | Placebo |
|---|---|---|---|---|
| Change in Shortness of Breath (SOB) Score | 2.1 ± 10.3 | 1.5 ± 5.7 | 3.3 ± 11.6 | -3.0 ± 9.8 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Sildenafil | 0/9 (0%) | 0/9 (0%) | 7/9 (77.8%) |
| Losartan | 1/12 (8.3%) | 1/12 (8.3%) | 9/12 (75%) |
| Sildenafil and Losartan | 0/9 (0%) | 1/9 (11.1%) | 7/9 (77.8%) |
| Placebo | 0/10 (0%) | 1/10 (10%) | 5/10 (50%) |
| Event | Sildenafil | Losartan | Sildenafil and Losartan | Placebo |
|---|---|---|---|---|
| Chest PainCardiac disorders | 0/9 | 1/12 | 1/9 | 1/10 |
| Idiopathic Pulmonary Fibrosis ExacerbationRespiratory, thoracic and mediastinal disorders | 0/9 | 1/12 | 0/9 | 0/10 |
| Event | Sildenafil | Losartan | Sildenafil and Losartan | Placebo |
|---|---|---|---|---|
| Respiratory infection/viral illnessRespiratory, thoracic and mediastinal disorders | 2/9 | 1/12 | 5/9 | 2/10 |
| CoughRespiratory, thoracic and mediastinal disorders | 1/9 | 5/12 | 3/9 | 2/10 |
| FlushingSkin and subcutaneous tissue disorders | 3/9 | 1/12 | 0/9 | 1/10 |
| HeadacheNervous system disorders | 3/9 | 0/12 | 1/9 | 1/10 |
| Gastroesophageal RefluxGastrointestinal disorders | 1/9 | 0/12 | 2/9 | 0/10 |
| HypotensionVascular disorders | 0/9 | 1/12 | 1/9 | 0/10 |
| EdemaCardiac disorders | 1/9 | 1/12 | 0/9 | 0/10 |
| PneumoniaRespiratory, thoracic and mediastinal disorders | 0/9 | 0/12 | 1/9 | 0/10 |
| Urinary Tract InfectionRenal and urinary disorders | 0/9 | 1/12 | 1/9 | 0/10 |
| SinusitisEar and labyrinth disorders | 0/9 | 1/12 | 0/9 | 1/10 |
Subjects were randomized to complete all four arms in random order. There were nine participants analyzed in the study and all nine of those subjects participated in each arm. The numbers above do not include the 3 withdrawn subjects that did not complete the arms.
| Age, Continuous(years) | All Study Participants |
|---|---|
| Mean | 63 (45 to 76) |
| Sex: Female, Male(Participants) | All Study Participants |
|---|---|
| Female | 4 |
| Male | 5 |
| Race (NIH/OMB)(Participants) | All Study Participants |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 9 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(Participants) | All Study Participants |
|---|---|
| United States | 9 |
Plan to share: No
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