E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
perioperative inflammation in patients undergoing oesophagectomy. |
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E.1.1.1 | Medical condition in easily understood language |
patients who need surgery for oesophageal cancer are at high risk of post-operative inflammation and lung damage due to the extent and duration of the surgery. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
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 |
The aim of this study is to establish whether giving patients undergoing removal of the oesophagus for cancer vitamin d as a single dose reduces the inflammation and lung damage that occurs as a result of the surgical trauma. The primary outcome measure is the increase in lung water pre-post operative comparing dummy drug (placebo) with vitamin D. This is a marker of lung damage that is increased in patients following oesophagectomy. |
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E.2.2 | Secondary objectives of the trial |
Secondary outcomes are safety and tolerability data- blood biochemistry, medication related side effects as well as markers of inflammation in the blood and bronchoalveolar lavage fluid that may be influenced by vitamin d. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• • Planned transthoracic oesophagectomy for oesophageal carcinoma at a participating centre. • Men aged over 18 years on day of first dose of IMP • Women over the age of 55 or more than 2 years since menopause. • Women of potential child bearing age (under 55 and less than 2 years since menopause) may be recruited provided they agree to use contraception during the pre- post operative period (8 weeks). • Ability to give written informed consent to participate in the study. |
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E.4 | Principal exclusion criteria |
• known intolerance of vitamin D. • known sarcoidosis, hyperparathyroidism, or nephrolithiasis. • taking more than 1000iu/day vitamin D supplementation in the month preceding enrolment. • known serum corrected calcium >2.65 mmol/L. • undergoing haemodialysis. • Pregnant or breastfeeding. • Taking cardiac glycoside, carbamazepine, phenobarbital, phenytoin, primidone or long-term immunosuppressant therapy. • Patients taking benzothiadiazine derivatives at doses higher than that which is recommended in the BNF • Patients taking benzothiadiazine derivative in combination with a calcium supplement • Patients with tuberculosis or lymphoma. • Individuals taking a dietary supplement containing > 1000 IU of vitamin D/day up to 1 months before first dose of IMP vitamin D will not be eligible to participate in the study and must not take additional supplements for the duration of the trial. • Diagnosis of COPD with an FEV1 less than 50% predicted or resting oxygen saturations of less 92%. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Post-operative extrascular lung water index. This will be measured at the end of the operation once one lung ventilation has ceased. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
This will be assessed at the start of the operation, at the end (primary outcome) and daily post-operatively whilst the necessary central and arterial lines are in situ. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints are: 1) Clinical markers indicative of lung injury: P:F ratio, oxygenationindex, development of lung injury / ARDS day 0-28, duration of ventilation and organ failure,survival). 2) Safety and tolerability of vitamin D supplementation. 3) Plasma indices of endothelial and alveolar epithelial function/ injury. 4) Plasma inflammatory response. 5) Plasma LL-37 levels 6) plasma vitamin D status (25D3, 1,25D3 and VDBP) 7) EVLWI post-operative day 1 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
preoperatively, post-operatively, and day 1 post-operatively. |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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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The end of the study will be defined as the date of the final day of the final participant undergoing follow-up. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |