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    Summary
    EudraCT Number:2007-000446-12
    Sponsor's Protocol Code Number:CRO826
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2008-03-26
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2007-000446-12
    A.3Full title of the trial
    Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy
    A.3.2Name or abbreviated title of the trial where available
    Walk PHaSST
    A.4.1Sponsor's protocol code numberCRO826
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorImperial College London
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Revatio
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameSildenafil
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSILDENAFIL CITRATE
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameSildenafil
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSildenafil Citrate
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number80
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Pulmonary hypertension associated with sickle cell disease
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    In a randomised, double-blind, placebo-controlled phase II/III trial, to determine the efficacy of 16 weeks of sildenafil therapy on exercise capacity (six-minute walk distance).
    E.2.2Secondary objectives of the trial
    1.To determine the efficacy of 16 weeks of sildenafil therapy on echocardiographic estimates of right ventricular systolic pressure, and symptoms in patients with sickle cell disease and pulmonary hypertension.
    2.In subjects with more severe pulmonary hypertension (TRV greater than or equal to 3.0 m/sec stratum), to evaluate and compare the acute haemodynamic effects of inhaled nitric oxide and of oral sildenafil and to determine the changes in hemodynamics after 16 weeks of sildenafil therapy
    3.To determine the safety of 16 weeks of sildenafil therapy via adverse event reports and laboratory assessments
    4.To evaluate prospective clinical outcomes in the subjects participating in the Observational Follow-up Study to the extent possible by each participating site
    5.To provide subjects with open-label sildenafil for up to one year after completion of the Main Interventional Trial and to evaluate the long term safety of sildenafil in this population
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Males or females, greater than or equal to 12 years of age and less than or
    equal to 70 years of age
    2. For female subjects, on a reliable method of birth control or not physically
    able to bear children
    3. Electrophoretic documentation of sickle cell disease (including, but not
    limited to SS, SC, SD, or Sβ°/+ thalassemia)
    4. At least mild pulmonary hypertension with TRV ≥ 2.7 m/s by
    echocardiogram
    5. Six minute walk distance of 150-500 m
    6. In the opinion of the investigator, ability to complete the protocol scheduled
    assessments during the 16 week, double-blind phase
    7. Provision of informed consent and, where applicable, assent
    8. Subjects with systemic hypertension must be on a stable antihypertensive
    regimen for greater than or equal to 90 days and a stable dose for greater than
    or equal to 30 days.
    E.4Principal exclusion criteria
    1. Current pregnancy or lactation
    2. Any one of the following medical conditions:
    • Stroke within the last six weeks
    • New diagnosis of pulmonary embolism within the last three months
    • History of retinal detachment or retinal hemorrhage in the last 6 months
    • Non-arteritic anterior ischemic optic neuropathy (NAION) in one or both eyes
    • History of sustained priapism requiring medical or surgical treatment, unless
    currently impotent or on transfusion program within the last two years
    • Any unstable (chronic or acute) condition that in the opinion of the
    investigator will prevent completion of the study
    3. Subjects taking nitrate-based vasodilators (including, but not limited to
    nicorandil [available in the UK only] ), prostacyclin (inhaled, subcutaneous or
    intravenous) or endothelin antagonists. Subjects taking calcium channel
    blockers will be allowed to participate provided they are on a stable dose for ≥
    3 months.
    4. Left ventricular ejection fraction < 40% or clinically significant ischemic,
    valvular or constrictive heart disease: LVEF <40% or SF < 22%
    5. Subjects who are in other research studies with investigational drugs, with the
    exception of hydroxyurea, unless the other trial has been approved by the
    walk-PHaSST Executive Committee for co-participation
    6. Acute or chronic impairment (other than dyspnea), limiting the ability to
    comply with study requirements (in particular with 6MWT), e.g., angina
    pectoris, intermittent claudication, symptomatic hip osteonecrosis
    7. Tonsillectomies for sleep apnea within 3 months prior to randomization
    8. Active therapy for pulmonary hypertension, including prostacyclin analog,
    endothelin-1 antagonists, or PDE-5 inhibitor
    9. Protease inhibitor therapy for the treatment of HIV
    10. Subjects taking potent CYP3A4 inhibitor therapy (e.g., itraconazole, ritonavir,
    ketoconazole)
    11. Subjects who are anticoagulated and have proliferative retinopathy (unless
    they have had ophthalmologist recommended intervention (e.g., phototherapy)
    or have been otherwise cleared by an ophthalmologist to participate in the
    study)
    12. Subjects with systolic blood pressure greater than or equal to 140 mmHg OR
    diastolic blood pressure greater than or equal to 90 mmHg. See Section 9.3.3
    for qualifying blood pressure assessment instructions.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy hypothesis is that 16 weeks of sildenafil therapy provides greater improvement in six-minute walk (6MW) distance than does placebo in patients with sickle cell disease (SCD) and pulmonary hypertension.
    The primary efficacy analysis is an Analysis of Covariance Analysis (ANCOVA) on 6MW distance change from baseline to Week 16 on the Intent to Treat (ITT) Population. The primary hypothesis test will be based on a test that the average change differs between the two treatment groups, with baseline 6MW distance and TRV stratum used as covariates. This type of model controls for any impact of baseline 6MW on the treatment effect without assumptions about the slope of the relationship between the baseline and Week 16 measures.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    two phases: an initial 16 week randomized study followed by 1 year open label safety study
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Completion of the 16 week randomized trial by 132 patients plus completion of the 1 year observational follow-up study on open-label sildenafil.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Subjects will have a diagnosis of sickle cell disease and will be age 12 years or older. Women of child bearing age must be established on contraception before participating in the trial or not physically able to bear children.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state22
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 22
    F.4.2.2In the whole clinical trial 132
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    After the 16 week randomised trial subjects who complete this phase will be offered open-label sildenafil for one additional year.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2007-11-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-12-14
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2009-07-08
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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