E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Dysfunction of the lungs after open heart surgery. |
Dysfunktion af lungerne efter åben hjertekirurgi. |
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E.1.1.1 | Medical 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. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main 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). |
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E.2.2 | Secondary 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.
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- 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary 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). |
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E.5.1.1 | Timepoint(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.
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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. |
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E.5.2 | Secondary 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. |
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E.5.2.1 | Timepoint(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.
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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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial 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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |