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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-022460-12 | EudraCT Number | ||
| 2007-58-0015/HEH.750.89-12 | Other Identifier | The Danish Data Protection Agency | |
| H-4-2011-007 | Other Identifier | The Danish Ethics Committee |
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Inclusion rate not as expected. Not financially possible to involve other centres.
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| Name | Class |
|---|---|
| University of Copenhagen | OTHER |
| Rigshospitalet, Denmark | OTHER |
| Pharma Nord | INDUSTRY |
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The purpose of this study is to investigate the effect of 6 mg melatonin daily for 1 week preoperatively to 12 weeks postoperatively on depressive symptoms, anxiety, cognitive function and sleep disturbances in breast cancer patients. Furthermore the investigators will examine whether a specific clock-gene (HPER3) is correlated with an increased risk of depression, sleep disturbances or cognitive dysfunction.
About 1.4 million women are diagnosed with breast cancer every year. Breast cancer is the most common malignancy among women worldwide constituting about 1/5 of all cancer types. Breast cancer diagnosis and treatment, and the months following primary therapy are stressful times for most women. Aside from the actual "cancer threat" many women experience various degrees of depression, anxiety, sleep disturbances and memory/concentration problems (cognitive dysfunction). Naturally these factors influence the quality of life but also contribute to morbidity and mortality.
Melatonin is a regulatory circadian hormone having, among others, hypnotic, sedative, anxiolytic and possibly anti-depressive effects. It has very low toxicity and very few adverse effects.
The purpose of this project is to test melatonin (6 mg daily for 1 week preoperatively to 12 weeks postoperatively) on breast cancer patients and hopefully hereby be able to prevent depression, anxiety, sleep disturbances and cognitive dysfunction. On an overall perspective this will hopefully contribute to improving the quality of life for these patients and extend their lifetime. Furthermore the investigators will be examining whether a specific gene called a clock-gene (HPER3) is correlated with an increased risk of depression, sleep disturbances or cognitive dysfunction. If this is the case it could become possible to identify women with an increased risk and provide prophylactic treatment for those with a risk of developing a depression, sleep disturbances or cognitive disturbances.
Sample size calculations were based on our primary outcome parameter. Using a conservative estimate for the incidence of depression, the investigators expect to find a reduction from 30% to 15% with melatonin treatment. Sample size is sufficient to include our secondary and tertiary outcome parameters as well. The sample size calculations were calculated with a power of 80%, a type I error of 5% and a type II error of 20%.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Melatonin | Active Comparator | 6 mg oral melatonin daily |
|
| Placebo | Placebo Comparator | 6 mg oral placebo daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Melatonin (N-acetyl-5-methoxytryptamine) | Drug | 6 mg oral melatonin daily 1 hour before bedtime |
|
| Measure | Description | Time Frame |
|---|---|---|
| Major Depression Inventory (MDI)- Depression at One Point in the Study | MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used either as a rating scale or diagnostic instrument. For inclusion we used the diagnostic instrument (depression was an exclusion criteria) and for all other MDI measurements we used the rating scale. Diagnostic scale using the ICD-10 algorithm: Mild depression: 2 core symptoms and 2 other symptoms Moderate depression: 2 core symptoms and 4 other symptoms Severe depression: 3 core symptoms and 5 other symptoms Rating scale: No depression - score from 0-20 Mild depression - score from 21-25 Moderate depression - score from 26-30 Severe depression - score from 31-50 | Depression at one point in the study (not including baseline) out of 4 measurements at app. day 21, day 35, day 63 and day 91 of the study. |
| Per Protocol - Depression at One Point in the Study Period | MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used either as a rating scale or diagnostic instrument. For inclusion we used the diagnostic instrument (depression was an exclusion criteria) and for all other MDI measurements we used the rating scale. Rating scale: No depression - score from 0-20 Mild depression - score from 21-25 Moderate depression - score from 26-30 Severe depression - score from 31-50 This analysis includes only patients who have taken study medication as planned. | Per protocol - depression at one point in the study period (not baseline) |
| Intention to Treat (Underestimate) - Depression at One Point in the Study Period | MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used either as a rating scale or diagnostic instrument. For inclusion we used the diagnostic instrument (depression was an exclusion criteria) and for all other MDI measurements we used the rating scale. Rating scale: No depression - score from 0-20 Mild depression - score from 21-25 Moderate depression - score from 26-30 Severe depression - score from 31-50 For this analysis all missing MDI data have been analyzed as "NO" depression. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve (AUC) for VAS Data on Anxiety - Immediate Postoperative Period | Anxiety measured by VAS (visual analog scale). A subjective feeling of anxiety was registered on a VAS going from "no anxiety", equivalent to 0mm to "worst possible anxiety", equivalent to 100mm. Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively. Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 % |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Melissa V Hansen, MD | Herlev Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Herlev Hospital | Copenhagen | 2730 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25328711 | Derived | Hansen MV, Madsen MT, Andersen LT, Hageman I, Rasmussen LS, Bokmand S, Rosenberg J, Gogenur I. Effect of Melatonin on Cognitive Function and Sleep in relation to Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial. Int J Breast Cancer. 2014;2014:416531. doi: 10.1155/2014/416531. Epub 2014 Aug 27. |
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The recruitment period was from July 2011 till December 2012. The location was The Department of Breast Surgery - Herlev Hospital, Copenhagen - Denmark.
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| ID | Title | Description |
|---|---|---|
| FG000 | Melatonin | 6 mg oral melatonin daily |
| FG001 | Placebo | 6 mg oral placebo daily |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Melatonin | 6 mg oral melatonin daily |
| BG001 | Placebo | 6 mg oral placebo daily |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Major Depression Inventory (MDI)- Depression at One Point in the Study | MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used either as a rating scale or diagnostic instrument. For inclusion we used the diagnostic instrument (depression was an exclusion criteria) and for all other MDI measurements we used the rating scale. Diagnostic scale using the ICD-10 algorithm: Mild depression: 2 core symptoms and 2 other symptoms Moderate depression: 2 core symptoms and 4 other symptoms Severe depression: 3 core symptoms and 5 other symptoms Rating scale: No depression - score from 0-20 Mild depression - score from 21-25 Moderate depression - score from 26-30 Severe depression - score from 31-50 | Includes all patients who have completed at least one other MDI than baseline | Posted | Number | participants | Depression at one point in the study (not including baseline) out of 4 measurements at app. day 21, day 35, day 63 and day 91 of the study. |
From inclusion (app. 1 week preoperatively) till the final visit (app. 10 weeks postoperatively)
Only includes patients who have at least taken 1 dose of the study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Melatonin | 6 mg oral melatonin daily |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders |
Premature termination (54/260). Only included about 8% (54/703) of the patients assessed for eligibility.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| MD Melissa Voigt Hansen | Herlev Hospital, Department of Surgery | +45 20661119 | melissa.voigt.hansen@regionh.dk |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D003863 | Depression |
| D001008 | Anxiety Disorders |
| D020447 | Parasomnias |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D008550 | Melatonin |
| ID | Term |
|---|---|
| D014363 | Tryptamines |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Placebo | Drug | 6 mg oral placebo daily 1 hour before bedtime |
|
| Intention to treat (underestimate) - depression at one point in the study period (not baseline) |
| Intention to Treat (Overestimate) - Depression at One Point in the Study Period | MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used either as a rating scale or diagnostic instrument. For inclusion we used the diagnostic instrument (depression was an exclusion criteria) and for all other MDI measurements we used the rating scale. Rating scale: No depression - score from 0-20 Mild depression - score from 21-25 Moderate depression - score from 26-30 Severe depression - score from 31-50 For this analysis all missing MDI data have been analyzed as "YES" for depression. | Intention to treat (overestimate) - depression at one point in the study period (not baseline) |
| Daily - from inclusion till 8 days postoperatively |
| Area Under the Curve (AUC) for VAS Data on Anxiety - Long-term Postoperative Period | Anxiety measured by VAS (visual analog scale). Completed every 14th day. A subjective feeling of anxiety was registered on a VAS going from "no anxiety", equivalent to 0mm to "worst possible anxiety", equivalent to 100mm. Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day). Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 % | App. 14 days postoperatively till 10 weeks postoperatively |
| Area Under the Curve (AUC) for Data on Sleepiness (KSS) - Immediate Postoperative Period | Sleepiness measured by Karolinska Sleepiness Scale. KSS is a 9-point scale from 1 (very awake) to 9 (very sleepy) where a score of 7 or more reflects pathological sleepiness. Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively. Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 % | Daily from inclusion till 8 days postoperatively |
| Area Under the Curve (AUC) for Data on Sleepiness (KSS) - Long-term Postoperative Period | Sleepiness measured by Karolinska Sleepiness Scale. KSS is a 9-point scale from 1 (very awake) to 9 (very sleepy) where a score of 7 or more reflects pathological sleepiness. Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day). Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 % | App. 14 days postoperatively till 10 weeks postoperatively |
| Area Under the Curve (AUC) for VAS Data on Fatigue - Immediate Postoperative Period | Fatigue on a Visual Analog Scale - filled out daily. A subjective feeling of fatigue was registered on a VAS going from "no fatigue", equivalent to 0mm to "worst possible fatigue", equivalent to 100mm. Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively. Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 % | Daily from inclusion till 8 days postoperatively |
| Area Under the Curve (AUC) for VAS Data on Fatigue - Long-term Postoperative Period | Fatigue on a Visual Analog Scale - filled out every 14th day. A subjective feeling of fatigue was registered on a VAS going from "no fatigue", equivalent to 0mm to "worst possible fatigue", equivalent to 100mm. Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day). Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 % | App. 14 days postoperatively till 10 weeks postoperatively |
| Area Under the Curve (AUC) for Data on General Well-being - Immediate Postoperative Period | General well-being on a Visual Analog Scale - filled out daily. A subjective feeling of general well-being was registered on a VAS going from "very high well-being", equivalent to 0mm to "very low well-being", equivalent to 100mm. Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively. Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 % | Daily from inclusion till 8 days postoperatively |
| Area Under the Curve (AUC) for VAS Data on General Well-being - Long-term Postoperative Period | General well-being on a Visual Analog Scale - filled out every 14th day. A subjective feeling of general well-being was registered on a VAS going from "very high well-being", equivalent to 0mm to "very low well-being", equivalent to 100mm. Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day). Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 % | App. 14 days postoperatively till 10 weeks postoperatively |
| Area Under the Curve (AUC) for VAS Data on Pain - Immediate Postoperative Period | Pain on a Visual Analog Scale - filled out daily. A subjective feeling of pain was registered on a VAS going from "no pain", equivalent to 0mm to "worst possible pain", equivalent to 100mm. Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively. Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 % | Daily from inclusion till 8 days postoperatively |
| Area Under the Curve (AUC) for VAS Data on Pain - Long-term Postoperative Period | Pain on a Visual Analog Scale - filled out every 14th day. A subjective feeling of pain was registered on a VAS going from "no pain", equivalent to 0mm to "worst possible pain", equivalent to 100mm. Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day). Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 % | App. 14 days postoperatively till 10 weeks postoperatively |
| Area Under the Curve (AUC) for VAS Data on Sleep Quality - Immediate Postoperative Period | Subjective sleep score on Visual Analog Scale. Subjective sleep quality was registered on a VAS going from "best possible sleep", equivalent to 0mm to "worst possible sleep", equivalent to 100mm. Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively. Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 % | Daily from inclusion till 8 days postoperatively |
| Area Under the Curve (AUC) for VAS Data on Sleep Quality - Long-term Postoperative Period | Subjective sleep on a Visual Analog Scale. Subjective sleep quality was registered on a VAS going from "best possible sleep", equivalent to 0mm to "worst possible sleep", equivalent to 100mm. Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day). Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 % | App. 14 days postoperatively till 10 weeks postoperatively |
| Sleep Architecture | Actigraphy (total minutes asleep, sleep effectiveness, sleep latency, awakenings). A wrist actigraph will be worn from inclusion till 14 days postoperatively. | From inclusion till 14 days postoperatively |
| HPER3 Genotype | A blood sample will be taken at inclusion and analysed for HPER3 genotype (4/4, 4/5, 5/5) and this will be investigated for a correlation with sleep, cognitive function and depressive symptoms 7 patients did not give blood samples | At inclusion = day-7 |
| Incidence of Postoperative Cognitive Dysfunction (POCD) App. 2 Weeks Postoperatively. | Calculations for POCD were based on normative data from 133 females aged 40-60 years. We evaluated changes from the preoperative baseline to the 2 postoperative test sessions. In controls we calculated mean and standard deviations (SD) of these differences. The mean change in this group may be taken as estimated learning effects. For the individual patients, we compared baseline scores with the 2- and 12-week postoperative test results, subtracted the average learning effect from the changes and divided the result by the SD of the control group to obtain a Z score for the 7 individual test outcomes. A large positive Z score indicated deterioration in cognitive function from baseline in patients. We defined a composite Z score as the sum of the 7 Z scores and normalized this using the SD for that sum in the controls. POCD was defined as a combined Z score >1.96 or a Z score >1.96 in at least 2 of the 7 subtests. Units of measure = % of patients with YES to POCD | App. 2 weeks postoperatively |
| Incidence of Postoperative Cognitive Dysfunction (POCD) App. 10 Weeks Postoperatively | Calculations for POCD were based on normative data from 133 females aged 40-60 years. We evaluated changes from the preoperative baseline to the 2 postoperative test sessions. In controls we calculated mean and standard deviations (SD) of these differences. The mean change in this group may be taken as estimated learning effects. For the individual patients, we compared baseline scores with the 2- and 12-week postoperative test results, subtracted the average learning effect from the changes and divided the result by the SD of the control group to obtain a Z score for the 7 individual test outcomes. A large positive Z score indicated deterioration in cognitive function from baseline in patients. We defined a composite Z score as the sum of the 7 Z scores and normalized this using the SD for that sum in the controls. POCD was defined as a combined Z score >1.96 or a Z score >1.96 in at least 2 of the 7 subtests. Units of measure = % of patients with YES to POCD | App. 10 weeks postoperatively |
| Protocol Violation |
|
| Adverse Event |
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| BG002 |
| Total |
Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Type of surgery | SN: sentinel node | Number | Participants |
|
| Surgery duration | Median | Inter-Quartile Range | Minutes |
|
| Anaesthesia duration | Median | Inter-Quartile Range | Minutes |
|
| Oncological treatment | Only registered as which oncological treatment (if any at all) the patients received during their participation in the MELODY trial | Number | Participants |
|
| Anti-hormone therapy | Only registered as which anti-hormone therapy (if any at all) the patients received during their participation in the MELODY trial | Number | Participants |
|
| MDI - Major Depression Inventory | The MDI is a self-rating scale including 12 questions and has been validated in a Danish population. The MDI assesses information on depressive symptoms that have been present continuously during the previous 2 weeks. The individual items are measured on a 6-point Likert scale, ranging from 0 to 5, with graduations depending on the extent of the symptom the previous 14 days. Accordingly, the theoretical score ranges from 0 to 50. | Median | Inter-Quartile Range | Scores on a scale |
|
| Menopausal status | Number | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Melatonin | 6 mg oral melatonin daily |
| OG001 | Placebo | 6 mg oral placebo daily |
|
|
|
| Primary | Per Protocol - Depression at One Point in the Study Period | MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used either as a rating scale or diagnostic instrument. For inclusion we used the diagnostic instrument (depression was an exclusion criteria) and for all other MDI measurements we used the rating scale. Rating scale: No depression - score from 0-20 Mild depression - score from 21-25 Moderate depression - score from 26-30 Severe depression - score from 31-50 This analysis includes only patients who have taken study medication as planned. | Includes only patients who have taken the study medication as planned | Posted | Number | participants | Per protocol - depression at one point in the study period (not baseline) |
|
|
|
|
| Primary | Intention to Treat (Underestimate) - Depression at One Point in the Study Period | MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used either as a rating scale or diagnostic instrument. For inclusion we used the diagnostic instrument (depression was an exclusion criteria) and for all other MDI measurements we used the rating scale. Rating scale: No depression - score from 0-20 Mild depression - score from 21-25 Moderate depression - score from 26-30 Severe depression - score from 31-50 For this analysis all missing MDI data have been analyzed as "NO" depression. | All missing MDI data have been analyzed as "NO" depression. | Posted | Number | participants | Intention to treat (underestimate) - depression at one point in the study period (not baseline) |
|
|
|
|
| Primary | Intention to Treat (Overestimate) - Depression at One Point in the Study Period | MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used either as a rating scale or diagnostic instrument. For inclusion we used the diagnostic instrument (depression was an exclusion criteria) and for all other MDI measurements we used the rating scale. Rating scale: No depression - score from 0-20 Mild depression - score from 21-25 Moderate depression - score from 26-30 Severe depression - score from 31-50 For this analysis all missing MDI data have been analyzed as "YES" for depression. | All missing data have been analyzed as "YES" depression. | Posted | Number | participants | Intention to treat (overestimate) - depression at one point in the study period (not baseline) |
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|
|
| Secondary | Area Under the Curve (AUC) for VAS Data on Anxiety - Immediate Postoperative Period | Anxiety measured by VAS (visual analog scale). A subjective feeling of anxiety was registered on a VAS going from "no anxiety", equivalent to 0mm to "worst possible anxiety", equivalent to 100mm. Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively. Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 % | Posted | Median | Inter-Quartile Range | mm*day | Daily - from inclusion till 8 days postoperatively |
|
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|
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| Secondary | Area Under the Curve (AUC) for VAS Data on Anxiety - Long-term Postoperative Period | Anxiety measured by VAS (visual analog scale). Completed every 14th day. A subjective feeling of anxiety was registered on a VAS going from "no anxiety", equivalent to 0mm to "worst possible anxiety", equivalent to 100mm. Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day). Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 % | Patients were only included in the analysis if they had completed VAS on anxiety in the long-term postoperative period. Single missing data were filled out using last observation carried forward. | Posted | Median | Inter-Quartile Range | mm*2 weeks | App. 14 days postoperatively till 10 weeks postoperatively |
|
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|
|
| Secondary | Area Under the Curve (AUC) for Data on Sleepiness (KSS) - Immediate Postoperative Period | Sleepiness measured by Karolinska Sleepiness Scale. KSS is a 9-point scale from 1 (very awake) to 9 (very sleepy) where a score of 7 or more reflects pathological sleepiness. Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively. Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 % | Posted | Median | Inter-Quartile Range | Units on KSS*day | Daily from inclusion till 8 days postoperatively |
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| Secondary | Area Under the Curve (AUC) for Data on Sleepiness (KSS) - Long-term Postoperative Period | Sleepiness measured by Karolinska Sleepiness Scale. KSS is a 9-point scale from 1 (very awake) to 9 (very sleepy) where a score of 7 or more reflects pathological sleepiness. Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day). Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 % | Posted | Median | Inter-Quartile Range | Units on KSS*2 weeks | App. 14 days postoperatively till 10 weeks postoperatively |
|
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|
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| Secondary | Area Under the Curve (AUC) for VAS Data on Fatigue - Immediate Postoperative Period | Fatigue on a Visual Analog Scale - filled out daily. A subjective feeling of fatigue was registered on a VAS going from "no fatigue", equivalent to 0mm to "worst possible fatigue", equivalent to 100mm. Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively. Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 % | Posted | Median | Inter-Quartile Range | mm*day | Daily from inclusion till 8 days postoperatively |
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| Secondary | Area Under the Curve (AUC) for VAS Data on Fatigue - Long-term Postoperative Period | Fatigue on a Visual Analog Scale - filled out every 14th day. A subjective feeling of fatigue was registered on a VAS going from "no fatigue", equivalent to 0mm to "worst possible fatigue", equivalent to 100mm. Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day). Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 % | Posted | Median | Inter-Quartile Range | mm*2 weeks | App. 14 days postoperatively till 10 weeks postoperatively |
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| Secondary | Area Under the Curve (AUC) for Data on General Well-being - Immediate Postoperative Period | General well-being on a Visual Analog Scale - filled out daily. A subjective feeling of general well-being was registered on a VAS going from "very high well-being", equivalent to 0mm to "very low well-being", equivalent to 100mm. Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively. Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 % | Patients were only included in the analysis if they had completed daily VAS on anxiety for at least 8 days postoperatively. Single missing data were filled out using last observation carried forward. | Posted | Median | Inter-Quartile Range | mm*day | Daily from inclusion till 8 days postoperatively |
|
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| Secondary | Area Under the Curve (AUC) for VAS Data on General Well-being - Long-term Postoperative Period | General well-being on a Visual Analog Scale - filled out every 14th day. A subjective feeling of general well-being was registered on a VAS going from "very high well-being", equivalent to 0mm to "very low well-being", equivalent to 100mm. Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day). Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 % | Posted | Median | Inter-Quartile Range | mm*2 weeks | App. 14 days postoperatively till 10 weeks postoperatively |
|
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| Secondary | Area Under the Curve (AUC) for VAS Data on Pain - Immediate Postoperative Period | Pain on a Visual Analog Scale - filled out daily. A subjective feeling of pain was registered on a VAS going from "no pain", equivalent to 0mm to "worst possible pain", equivalent to 100mm. Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively. Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 % | Posted | Median | Inter-Quartile Range | mm*day | Daily from inclusion till 8 days postoperatively |
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| Secondary | Area Under the Curve (AUC) for VAS Data on Pain - Long-term Postoperative Period | Pain on a Visual Analog Scale - filled out every 14th day. A subjective feeling of pain was registered on a VAS going from "no pain", equivalent to 0mm to "worst possible pain", equivalent to 100mm. Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day). Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 % | Posted | Median | Inter-Quartile Range | mm*2 weeks | App. 14 days postoperatively till 10 weeks postoperatively |
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| Secondary | Area Under the Curve (AUC) for VAS Data on Sleep Quality - Immediate Postoperative Period | Subjective sleep score on Visual Analog Scale. Subjective sleep quality was registered on a VAS going from "best possible sleep", equivalent to 0mm to "worst possible sleep", equivalent to 100mm. Patients were only included in the analysis if they had completed daily VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness for at least 8 days postoperatively. Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 2 % | Posted | Median | Inter-Quartile Range | mm*day | Daily from inclusion till 8 days postoperatively |
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| Secondary | Area Under the Curve (AUC) for VAS Data on Sleep Quality - Long-term Postoperative Period | Subjective sleep on a Visual Analog Scale. Subjective sleep quality was registered on a VAS going from "best possible sleep", equivalent to 0mm to "worst possible sleep", equivalent to 100mm. Patients were only included in the analysis if they had completed VAS on anxiety, sleep quality, general well-being, fatigue, pain and sleepiness in the long-term postoperative period (every 14th day). Single missing data were filled out using last observation carried forward (LOCF). % of cases filled out by LOCF < 1 % | Posted | Median | Inter-Quartile Range | mm*2 weeks | App. 14 days postoperatively till 10 weeks postoperatively |
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| Secondary | Sleep Architecture | Actigraphy (total minutes asleep, sleep effectiveness, sleep latency, awakenings). A wrist actigraph will be worn from inclusion till 14 days postoperatively. | Not Posted | From inclusion till 14 days postoperatively |
| Secondary | HPER3 Genotype | A blood sample will be taken at inclusion and analysed for HPER3 genotype (4/4, 4/5, 5/5) and this will be investigated for a correlation with sleep, cognitive function and depressive symptoms 7 patients did not give blood samples | Posted | Number | Participants | At inclusion = day-7 |
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| Secondary | Incidence of Postoperative Cognitive Dysfunction (POCD) App. 2 Weeks Postoperatively. | Calculations for POCD were based on normative data from 133 females aged 40-60 years. We evaluated changes from the preoperative baseline to the 2 postoperative test sessions. In controls we calculated mean and standard deviations (SD) of these differences. The mean change in this group may be taken as estimated learning effects. For the individual patients, we compared baseline scores with the 2- and 12-week postoperative test results, subtracted the average learning effect from the changes and divided the result by the SD of the control group to obtain a Z score for the 7 individual test outcomes. A large positive Z score indicated deterioration in cognitive function from baseline in patients. We defined a composite Z score as the sum of the 7 Z scores and normalized this using the SD for that sum in the controls. POCD was defined as a combined Z score >1.96 or a Z score >1.96 in at least 2 of the 7 subtests. Units of measure = % of patients with YES to POCD | Analysis includes only patients who completed all parts of the neuropsychological test battery at baseline and 2 weeks postoperatively. | Posted | Number | Percentage of patients | App. 2 weeks postoperatively |
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| Secondary | Incidence of Postoperative Cognitive Dysfunction (POCD) App. 10 Weeks Postoperatively | Calculations for POCD were based on normative data from 133 females aged 40-60 years. We evaluated changes from the preoperative baseline to the 2 postoperative test sessions. In controls we calculated mean and standard deviations (SD) of these differences. The mean change in this group may be taken as estimated learning effects. For the individual patients, we compared baseline scores with the 2- and 12-week postoperative test results, subtracted the average learning effect from the changes and divided the result by the SD of the control group to obtain a Z score for the 7 individual test outcomes. A large positive Z score indicated deterioration in cognitive function from baseline in patients. We defined a composite Z score as the sum of the 7 Z scores and normalized this using the SD for that sum in the controls. POCD was defined as a combined Z score >1.96 or a Z score >1.96 in at least 2 of the 7 subtests. Units of measure = % of patients with YES to POCD | Analysis includes only patients who completed all parts of the neuropsychological test battery at baseline and 10 weeks postoperatively. | Posted | Number | Percentage of patients | App. 10 weeks postoperatively |
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| 0 |
| 27 |
| 15 |
| 27 |
| EG001 | Placebo | 6 mg oral placebo daily | 0 | 24 | 9 | 24 |
| Dizziness | Ear and labyrinth disorders |
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| Sleepiness | Nervous system disorders |
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| Difficulty falling asleep | General disorders |
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| More awakenings at night | General disorders |
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| Tiredness | General disorders |
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| Paraesthesia (mouth region, arms/legs) | Nervous system disorders |
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| Memory problems | Nervous system disorders |
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| Breathing difficulties | Respiratory, thoracic and mediastinal disorders |
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| Cough | Respiratory, thoracic and mediastinal disorders |
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| Pneumonia | Respiratory, thoracic and mediastinal disorders |
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| Atrial fibrillation | Cardiac disorders |
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| Nausea | Gastrointestinal disorders |
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| Reflux | Gastrointestinal disorders |
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| Abdominal pain | Gastrointestinal disorders |
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| Dry mouth | Skin and subcutaneous tissue disorders |
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| Obstipation | Gastrointestinal disorders |
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| Vomitus | Gastrointestinal disorders |
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| Diarrhoea | Gastrointestinal disorders |
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| Urinary urgency | Renal and urinary disorders |
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| Diffuse pain in the lower abdomen | Gastrointestinal disorders |
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| Lower back pain | Musculoskeletal and connective tissue disorders |
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| Joint pain | Musculoskeletal and connective tissue disorders |
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| Flushing/sweating | Skin and subcutaneous tissue disorders |
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| Itch (arms) | Musculoskeletal and connective tissue disorders |
|
Not provided
Not provided
| D017437 |
| Skin and Connective Tissue Diseases |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D001523 | Mental Disorders |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D006571 | Heterocyclic Compounds |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| 5/5 genotype |
|
| Missing |
|