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    The EU Clinical Trials Register currently displays   43974   clinical trials with a EudraCT protocol, of which   7312   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2011-006290-25
    Sponsor's Protocol Code Number:4141
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-05-02
    Trial 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 ConcernedDenmark - DHMA
    A.2EudraCT number2011-006290-25
    A.3Full title of the trial
    The Pulmonary Protection Trial (PP-Trial)

    Pulmonary dysfunction after open heart surgery: Randomized clinical trial with focus on lung-protective interventions
    The Pulmonary Protection Trial (PP-Trial)

    Pulmonal dysfunktion efter åben hjertekirurgi: Randomiseret klinisk forsøg med fokus på lungeprotektive interventioner
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Pulmonary dysfunction after open heart surgery: Clinical trial with focus on protecting of the lungs
    Lungedysfunktion efter åben hjertekirurgi: Klinisk forsøg med fokus på beskyttelse af lungerne
    A.3.2Name or abbreviated title of the trial where available
    The Pulmonary Protection Trial (PP-Trial)
    A.4.1Sponsor's protocol code number4141
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorCopenhagen University Hospital Rigshospitalet, The Heart Center - Department of Thoracic Surgery
    B.1.3.4CountryDenmark
    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 organisationCopenhagen University Hospital Rigshospitalet, The Heart Center - Department of Thoracic Anaesthesiology
    B.5.2Functional name of contact pointKatrine Bredahl Buggeskov
    B.5.3 Address:
    B.5.3.1Street AddressBlegdamsvej 9
    B.5.3.2Town/ cityCopenhagen
    B.5.3.3Post code2100
    B.5.3.4CountryDenmark
    B.5.4Telephone number004535459631
    B.5.6E-mailkatrine.buggeskov@gmail.com
    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 Custodiol HTK Solution (Histidine-tryptophan-ketoglutarate)
    D.2.1.1.2Name of the Marketing Authorisation holderDr. Franz Köhler Chemie
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameCustodiol HTK Solution
    D.3.2Product code SKS-kode 1301341
    D.3.4Pharmaceutical form Solution for perfusion of organs
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravascular use (Noncurrent)
    Intrapulmonary use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNHistidine-tryptophan-ketoglutarate
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    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 No
    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 Yes
    D.3.11.13.1Other medicinal product typeAs a crystalloid solution, Custodiol is considered an intracellular solution, i.e., electrolyte concentrations similar to an intracellular concentration.
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Dysfunction of the lungs after open heart surgery.
    Dysfunktion af lungerne efter åben hjertekirurgi.
    E.1.1.1Medical condition in easily understood language
    Impaired lung function, and hence oxidize ability, in patients who have undergone open heart surgery.
    Forringet lungefunktion, og deraf iltningsevne, hos patienter der har undergået åben hjertekirurgi.
    E.1.1.2Therapeutic area Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To investigate whether patients with a preoperative reduced pulmonary function have a better preserved oxygenation capacity after open heart surgery, using either pulmonary perfusion or pulmoplegia compared with TAVI and the control-group with standard ECC (Extra Corporal Circulation).
    At undersøge om patienter med præoperativ nedsat lungefunktion har en bedre bevaret oxygeneringsevne efter åben hjertekirurgi, ved anvendelse af enten pulmonal perfusion eller pulmoplegi sammenlignet med TAVI- og kontrolgruppen med standard ECC (ExtraCorporeal Circulation).
    E.2.2Secondary objectives of the trial
    - To investigate whether there is a difference in the postoperative oxygenation capacity in patients undergoing TAVI compared to open heart surgery, and to what extent this is due to the absence of the ECC triggered inflammatory response or a heart pump failure.
    - To investigate by an open lung biopsy, if there is a difference between the intervention groups compared to the TAVI and control group in the thickness of the wall and hence surface area of the alveoli as a cause of reduced oxygenation capacity.
    - Measuring, via a catheter placed in the right and the left atrium, the post-operative arterio-venous difference (AV difference) of the degree of activated alveolar macrophages (AMACs), white blood cells and other relevant inflammatory mediators of the intervention groups compared to TAVI and the control group, and biochemical analysis of differences in the inflammatory response of respectively the systemic and pulmonary circuit.
    - At undersøge om der er en forskel i den postoperative oxygeneringsevne hos patienter, der får fortaget TAVI sammenlignet med åben hjertekirurgi, og i hvor høj grad dette skyldes fraværet af det ECC udløste inflammatoriske respons eller et pumpesvigt.
    - At undersøge ved en åben lungebiopsi, om der er en forskel i alveolevæggens tykkelse og deraf overfladeareal for henholdsvis interventionsgrupperne overfor TAVI- og kontrolgruppen, som årsag til den nedsatte oxygeneringsevne.
    - At måle, via et kateter placeret i henholdsvis højre og venstre atrium, den postoperative arterio-venøse differens (AV-differensen) af graden af aktiveret alveolære makrofager (AMACs), leukocytter og andre relevante inflammatoriske mediatorer for interventionsgrupperne sammenlignet med TAVI- og kontrolgruppen, samt biokemiskanalyse af forskelle i det inflammatoriske respons for henholdsvis det systemiske og pulmonale kredsløb.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) Planned and urgent surgery on legally competent patients over 18 years:
    - Coronary Artery Bypass Graft Surgery
    - Aortic Valve Replacement
    - Coronary Artery Bypass Graft Surgery + Aortic Valve Replacement
    - Transcatheter Aortic-Valve Implantation

    2) Spirometry FEV1 measurement show less than or equal to 80% of the anticipated. We expect that these patients provide the largest signal with lung protective interventions in relation to lung healthy patients.
    1) Elektiv og subakut kirurgi på habile patienter over 18 år:

    - Coronary Artery Bypass Graft Surgery
    - Aortic Valve Replacement
    - Coronary Artery Bypass Graft Surgery + Aortic Valve Replacement
    - Transcatheter Aortic-Valve Implantation

    2) Spirometrimåling viser FEV1 under eller lig 80% af det forventet. Vi forventer, at disse patienter giver det største signal ved lungeprotektive interventioner i forhold til lungeraske patienter.
    E.4Principal exclusion criteria
    - Previous surgery on the heart or lungs
    - Previous thoracic irradiation
    - Preoperative heart failure (ejection fraction below 20%).
    - Surgical demanding mitral regurgitation
    - Unstable patients (heart rate above 100 and systolic blood pressure below 100 mmHg)
    - Intubated patients
    - Patients with an ongoing preoperative treatment with antibiotics for suspected pneumonia.
    - Patients with renal insufficiency requiring hemodialysis
    - Pregnant and lactating
    - Tidligere opereret i hjerte eller lunger
    - Tidligere thorakal bestråling
    - Præoperativ hjerteinsufficiens (Ejection Fraction under 20%).
    - Kirurgisk behandlingskrævende mitralinsufficiens
    - Ustabile patienter (puls over 100 og systolisk blodtryk under100 mmHg)
    - Intuberede patienter
    - Patienter, der præoperativt er i behandling med antibiotika for mistænkt pneumoni.
    - Patienter med hæmodialysekrævende nyreinsufficiens
    - Gravide og ammende
    E.5 End points
    E.5.1Primary end point(s)
    Selective pulmonary artery perfusion with oxygenated blood or pulmoplegia with Custodiol ® under the ECC can improve postoperative pulmonary function defined by the oxygenation index (OI) in patients that prior to open heart surgery have a reduced lung function (FEV1 below 80% of expected).
    Selektiv pulmonal perfusion med oxygeneret blod eller pulmoplegi med Custodiol® under ECC kan forbedre den postoperative lungefunktion defineret ved oxygenerings indekset (OI) hos patienter, der forud for åben hjertekirurgi, har en nedsat lungefunktion (FEV1 under 80% af det forventet).
    E.5.1.1Timepoint(s) of evaluation of this end point
    The trial is initiated June 2012. We will in the initial phase include 2 patients per week. When the logistics of the experiment is in place, and whit staff recruitment, will the inclusion rate increase to 4 patients per week. It is envisaged to include a total of 120 patients and complete their follow-up over a period of 1 1/2 years. The experiment is expected to be complete in September 2014, and time point of evaluation of end points September 2015.

    Forsøget indledes juni 2012. Vi vil i startfasen inkludere 2 patient per uge. Når logistikken i forsøget er på plads, og ved ansættelse af personale, vil vi øge inklusionsraten til 4 patienter om ugen. Det påtænkes at inkludere i alt 120 patienter og afslutte deres opfølgning over en periode på 1 1/2 år. Forventet tidspunkt for færdig evaluering af slutpunkt er juni 2016.
    E.5.2Secondary end point(s)
    - Intubation time is shortened in patients undergoing open heart surgery, when pulmonary perfusion or pulmoplegia is used intra-operatively compared to the control group, receiving ECC using current practice.

    - LOS ICU (Intensive Care Unit Length of Stay) will be reduced in patients undergoing open heart surgery, when used pulmonary perfusion or pulmoplegia intra-operatively compared to the control group with standard ECC.

    - TAVI patients have a better preserved postoperative lung function compared with the control group, since the lack of ECC gives a reduced immunological response.

    - The inflammatory response, including the degree of activation AMAC, is reduced in patients undergoing open heart surgery, when pulmonary perfusion or pulmoplegia i used intra-operatively compared to the control group with standard ECC.

    - The degree of uncoupling of oxidative phosphorylation in the mitochondria is reduced with use of pulmonary perfusion or pulmoplegia under the ECC, when compared with the control group.
    - Intubationstiden forkortes hos patienter, der undergår åben hjertekirurgi, når der peroperativt anvendes pulmonal perfusion eller pulmoplegi sammenlignet med kontrolgruppen, der får ECC efter aktuel praksis.

    - ICU-LOS (Intensive Care Unit Length of Stay) nedsættes hos patienter, der har fået foretaget åben hjertekirurgi, når der peroperativt anvendes pulmonal perfusion eller pulmoplegi sammenlignet med kontrolgruppen med standard ECC.

    - Patienter, der får fortaget TAVI, har en bedre bevaret postoperativ lungefunktion sammenlignet med kontrolgruppen, da fraværet af EEC giver et reduceret immunologisk respons.

    - Det inflammatoriske respons, herunder graden af AMAC aktivering, reduceres, når der under ECC anvendes enten pulmonal perfusion eller pulmoplegi sammenlignet med aktuel praksis.

    - Graden af afkoblingen af den oxidative phosphorylering i mitokondrierne nedsættes ved brug af pulmonal perfusion eller pulmoplegi under ECC, sammenlignet med kontrolgruppen.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The trial is initiated June 2012. We will in the initial phase include 2 patients per week. When the logistics of the experiment is in place, and whit staff recruitment, will the inclusion rate increase to 4 patients per week. It is envisaged to include a total of 120 patients and complete their follow-up over a period of 1 1/2 years. The experiment is expected to be complete in September 2014, and time point of evaluation of end points September 2015.

    Forsøget indledes juni 2012. Vi vil i startfasen inkludere 2 patient per uge. Når logistikken i forsøget er på plads, og ved ansættelse af personale, vil vi øge inklusionsraten til 4 patienter om ugen. Det påtænkes at inkludere i alt 120 patienter og afslutte deres opfølgning over en periode på 1 1/2 år. Forventet tidspunkt for færdig evaluering af slutpunkter er juni 2016.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety No
    E.6.5Efficacy No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States No
    E.8.5.1Number of sites anticipated in the EEA1
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    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) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 40
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 80
    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 No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation Yes
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state120
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 120
    F.4.2.2In the whole clinical trial 120
    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)
    Treatment according to current standards. No change.

    Behandling i henhold til gældende standarder. Ingen ændring.
    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 Decision2012-05-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-05-03
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-04-01
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