Pulmonary hypertension MedDRA version: 14.1 Level: PT Classification code 10037400 Term: Pulmonary hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Tiorfan
Product Name: Racecadotril
Pharmaceutical Form: Capsule
INN or Proposed INN: Racecadotril
CAS Number: 81110-73-8
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. WHO Group I pulmonary hypertension(i.e. idiopathic, familial or associated with connective tissue diseases) 2. 18-80 years old 3. Technically satisfactory right heart catheterisation (Step 1 only) 4. On sildenafil (20-100 mg; t.i.d.) 5. Six minute walk distance of equal to or >150 m at entry 6. No changes to PH specific therapies for 1 month 7. Not pregnant (women only). Women of childbearing potential only: Women must have a negative pregnancy test within seven days prior to being registered for trial treatment on day 0; they must be willing to use an effective method of contraception (including hormonal or barrier method of birth control) from the time consent is signed until six weeks after treatment discontinuation 8. Able to provide consent for the trial Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. Known sensitivity to racecadotril 2. Clinical diagnosis of liver cirrhosis or ALT/AST >two times the upper limit of normal 3. Kidney disease with an eGFR of <50 ml/min 4. History of angioedema 5. Systolic blood pressure <85 mmHg 6. Known history of drug or alcohol abuse within six months of enrolment 7. Participation in a clinical study involving another investigational drug 8. Women who are breastfeeding 9. Any clinical condition for which the investigator would consider the patient unsuitable for the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: There is one main aim: 1. To confirm that when racecadotril is administered to patients with pulmonary hypertension taking sildenafil, it inhibits the enzyme, neutral endopeptidase.;Secondary Objective: There are three main secondary aims: 1. To measure the effect of racecadotril, when administered to patients taking sildenafil, on blood pressure, including the blood pressure of the lungs (pulmonary artery pressure). 2. To measure the effect of racecadotril, when administered to patients taking sildenafil,on related blood biomarkers. 3. To assess the safety of racecadotril when administered to patients taking sildenafil.;Primary end point(s): Maximum percentage change from baseline in plasma atrial natriuretic peptide (ANP) concentration (nM).;Timepoint(s) of evaluation of this end point: Step 1: Blood samples taken at 0,1,2,3 and 6 hours (+/- 15 minutes/time point). Step 2: Blood samples taken on day 0 and on the 12th, or 13th, or 14th day of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Step 1 In patients with PH to determine the effect of a single dose of racecadotril or placebo (either 100 mg or 200 mg p.o). Racecadotril or placebo will be co-administered concurrently with sildenafil (20-100 mg; p.o.). 1. Pulmonary haemodynamic assessments: Maximum change in: 1. Pulmonary vascular resistance (dynes. sec/cm-5) 2. Stroke volume (ml) 3. Pulmonary artery occlusion pressure (mmHg) 4. Arterial saturation (%) 5. Mean arterial pressure (mmHg) 2. Systemic haemodynamic assessments: 1. Systolic and diastolic blood pressure (mmHg) and Heart Rate (BPM) 3. Additional biomarkers in the blood: Brain-type Natriuretic Peptide (BNP)(nM), N-terminal pro brain-type natriuretic peptide (NT-proBNP) (nM), C-type natriuretic peptide (CNP) (pM),Cyclic guanosine-3’,5’-monophosphate (cGMP) (nM), endothelin 1(ET-1) (nM), Nitrite and Nitrate (NOx) (nM) 4. Safety assessment: Adverse events Step 2 In patients with PH, to determine the effects of racecadotril or placebo administered in repeat dosing (100 or 200 mg t.i.d.) concurrently with sildenafil (20-100 mg; p.o.; t.i.d.) for 12, or 13, or 14 days, on; 1. Systemic haemodynamic assessments: Systolic and diastolic blood pressure (mmHg) and heart rate (BPM) 2. Additional biomarkers in the blood: Brain-type Natriuretic Peptide (BNP)(nM), N-terminal pro brain-type natriuretic peptide (NT-proBNP) (nM), C-type natriuretic peptide (CNP) (pM), Cyclic guanosine-3’,5’-monophosphate (cGMP) (nM) , endothelin 1(ET-1) (nM), Nitrite and Nitrate (NOx) (nM) 3. Safety assessment: Adverse events 4. Six minute walk test (m);Timepoint(s) of evaluation of this end point: Step 1: Pulmonary haemodynamics measured at 0, 1.5 and 2 hours (+/- 10 minutes /time point) Systemic haemodynamics measured at 0 and then every 30 minutes up to 6 hours (+/- 15 minutes /time point) Blood samples taken at 0,1,2,3 and 6 hours (+/- 15 minutes /time point). Step 2: Blood samples taken on day 0 and on the 12th, or 13th, or 14th d | — |
Countries
United Kingdom
Contacts
Public ContactUCL Clinical Trials Unit
University College London
Outcome results
None listed