Melatonin for Fatigue and Other Symptoms in Patients With Advanced Cancer

• Sponsor: Bispebjerg Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00925899
• Collaborator: I.M Daehnfeldt Foundation (Other), Danish Cancer Society (Other), Aase and Ejnar Danielsens Foundation (Other), Beckett Foundation (Other), The Andersen-Isted Foundation (Other)
• Enrollment: 72
• Location: 1
• Arms: 2
• Duration (Months): 41
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

BACKGROUND:

Patients with advanced cancer often suffer from fatigue and other symptoms and problems such as insomnia, appetite loss and pain. Problems that may have great consequences for their quality of life. Several studies suggest that a supplement of the hormone melatonin (MLT) may have a beneficial effect on these symptoms/problems. This needs further investigation.

AIM:

To investigate if a supplement of melatonin have an effect on a) fatigue (the primary outcome of the trial), b) the symptoms insomnia, appetite loss, depression and pain, and c) overall quality of life.

METHODS AND PATIENTS:

The trial takes place in the Department of Palliative Medicine, Bispebjerg Hospital, and 50 patients will participate. The participants have to be 18 years or above, have advanced cancer, and suffer from quite a bit or very much fatigue.

The study consists of two parts. In part I it is investigated if melatonin has a better effect than placebo on the outcomes mentioned above. This part is a consecutive, prospective, double blinded, randomized (MLT vs. placebo), cross-over study where the patients serve as their own control. In part II the effect of melatonin over time is investigated. Part II is a consecutive, prospective, open-label study.

The outcomes are assessed with weekly questionnaires (MFI-20 and EORTC QLQ-C15PAL) and a few daily diary questions.

Melatonin has been used in several studies, and the general conclusion is that it is a safe substance with few adverse drug reactions.

PERSPECTIVES:

If melatonin has the potential to alleviate fatigue and other symptoms in patients with advanced cancer and enhance the quality of life of these patients, this will be of benefit to many future patients. Trials such as this are important both nationally and internationally to develop an evidence-based palliative medicine.

Condition or Disease	Intervention/Treatment	Phase
Cancer; Fatigue	Drug: Melatonin; Drug: Placebo	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Melatonin for Fatigue and Other Symptoms in Patients With Advanced Cancer
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Melatonin 20 mg	Drug: Melatonin; 20 mg melatonin orally every evening about 1 hour before bedtime for one week. After having participated in the cross-over part of the trial (one week of melatonin followed by one week of placebo, or the other way around), the participant may receive melatonin for 6 weeks.
Placebo Comparator: Placebo	Drug: Placebo; Placebo tablet orally every evening about one hour before bedtime for one week. After having participated in the cross-over part of the trial (one week of placebo followed by one week of melatonin, or the other way around), the participant may receive melatonin for 6 weeks.

Outcome Measures

Primary Outcome Measures

1. Fatigue as Measured by the Physical Fatigue Scale in the The Multidimensional Fatigue Inventory (MFI) (Smets EM, Garssen B, Bonke B, et al., J Psychosom Res 39:315-325, 1995) [One week]

   Primary outcome: Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). The physical fatigue scale conists of four item each ranging from one to five. The four item were summed and the scae was converted to 0 to 100, where 100 indicated maximum fatigue.

Secondary Outcome Measures

1. Insomnia Measured by the Insomnia Item in the Questionnaire EORTC QLQ-C15-PAL [One week]

   Primary outcome: Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Insomnia was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated maximum insomnia.

2. Emotional Function as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006) [One week]

   Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Emotional function was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated the best possible emotional function. Note outcome reported for complete compliers

3. Pain as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006) [One week]

   Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Pain was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated maximum pain. Note outcome reported for complete compliers

4. Quality of Life as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006) [One week]

   Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Quality of Life was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated best possible quality of life. Note outcome reported for complete compliers

5. Appetite Loss as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006) [One week]

   Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Appetite loss was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated maximum appetite loss (worst possible). Note outcome reported for complete compliers

6. General Fatigue Measured by the The Multidimensional Fatigue Inventory (MFI) [One week]

   Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). The general fatigue scale that consits of four items was converted to a 0 til 100 scale where 100 indicated maximum (worst possible) fatigue. Note outcome reported for complete compliers

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Answered "quite a bit" or "very much" to the question "were you tired?" (from EORTC QLQ-C15-PAL)

• Cancer in a palliative phase

• Written informed consent

• Age 18 years or above

Exclusion Criteria:

• Not capable of understanding or judging information, or fill out a questionnaire

• Untreated anemia (Hb <= 6,0 mmol/L)

• Untreated hypocalcaemia

• Systolic blood pressure < 100

• In treatment with coumadin

• Receiving unstable doses of methylphenidate, corticosteroids or sleeping medicine the past two weeks

• TSH < 0.50 or > 5.50 mcL/mL

• Pregnant or breast feeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Palliative Medicine, Bispebjerg Hospital	Copenhagen		Denmark	2400

Sponsors and Collaborators

• Bispebjerg Hospital
• I.M Daehnfeldt Foundation
• Danish Cancer Society
• Aase and Ejnar Danielsens Foundation
• Beckett Foundation
• The Andersen-Isted Foundation

Investigators

• Principal Investigator: Lise Pedersen, MD, DMSc., Department of Palliative Medicine, Bispebjerg Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lise Pedersen, MD, DMSc, Bispebjerg Hospital
• ClinicalTrials.gov Identifier: NCT00925899
• Other Study ID Numbers: Feldt-01
• First Posted: Jun 22, 2009
• Last Update Posted: Apr 20, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Lise Pedersen, MD, DMSc, Bispebjerg Hospital: Melatonin; Palliative care; Advanced cancer; Symptoms; Quality of life; Randomized controlled trial
• Additional relevant MeSH terms: Fatigue; Melatonin

Study Results

Participant Flow

Pre-assignment Detail	72 patients were randomised in the study. 50 patients completed the first part of the stud, only 44 patients were complete compliers (having taking their melatonin and placebo for at least five days each week and having answered the questionnaires at all times). The primary analysis is of the 44 complete compliers.

Arm/Group Title	Part 1: Melatonin, Then Placebo	Part 1: Placebo, Then Melatonin
Arm/Group Description	First one week Melatonin: 20 mg melatonin orally every evening about 1 hour before bedtime for one week. Then one week Placebo: Placebo tablet orally every evening about one hour before bedtime for one week.	First one week Placebo: Placebo tablet orally every evening about one hour before bedtime for one week. Then one week Melatonin: 20 mg melatonin orally every evening about 1 hour before bedtime for one week.
Period Title: Part 1
STARTED	34	38
COMPLETED	23	27
NOT COMPLETED	11	11
Period Title: Part 1
STARTED	15	21
COMPLETED	9	9
NOT COMPLETED	6	12

Baseline Characteristics

Arm/Group Title	Melatonin, Then Placebo	Placebo. Then Melatonin	Total
Arm/Group Description	Melatonin then placebo: 20 mg melatonin orally every evening about 1 hour before bedtime for one week. Then 1 week placebo.	Placebo then melatonin: Placebo tablet orally every evening about one hour before bedtime for one week. Then one week melatonin 20 mg orally.	Total of all reporting groups
Overall Participants	34	38	72
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	65	62	63
Sex: Female, Male (Count of Participants)
Female	24 70.6%	25 65.8%	49 68.1%
Male	10 29.4%	13 34.2%	23 31.9%

Outcome Measures

1. Primary Outcome

Title	Fatigue as Measured by the Physical Fatigue Scale in the The Multidimensional Fatigue Inventory (MFI) (Smets EM, Garssen B, Bonke B, et al., J Psychosom Res 39:315-325, 1995)
Description	Primary outcome: Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). The physical fatigue scale conists of four item each ranging from one to five. The four item were summed and the scae was converted to 0 to 100, where 100 indicated maximum fatigue.
Time Frame	One week

Outcome Measure Data

Analysis Population Description

The primary analysis was a per protocol analysis including only complete compliers, defined as those patients who had consumed at least 5 capsules per week for the 2 weeks in part 1 and who had answered the MFI-20 on days 1, 7, 10, and 17.

Arm/Group Title	Melatonin Then Placebo	Placebo Then Melatonin
Arm/Group Description	20 mg Melatonin orally every evening about 1 hour before bedtime for one week. Then Placebo tablet orally every evening about one hour before bedtime for one week. Three days wash out in between.	Placebo tablet orally every evening about one hour before bedtime for one week. Then melatonin 20 mg melatonin orally every evening about 1 hour before bedtime for one week. Three days wash out in between.
Measure Participants	21	23
Mean (Standard Deviation) [units on a scale]	-1.1 (15.9)	-3.9 (18.1)

2. Secondary Outcome

Title	Insomnia Measured by the Insomnia Item in the Questionnaire EORTC QLQ-C15-PAL
Description	Primary outcome: Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Insomnia was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated maximum insomnia.
Time Frame	One week

Outcome Measure Data

Analysis Population Description

Complete compliers

Arm/Group Title	Melatonin Then Placebo	Placebo Then Melatonin
Arm/Group Description	20 mg Melatonin orally every evening about 1 hour before bedtime for one week. Then Placebo tablet orally every evening about one hour before bedtime for one week. Three days wash out in between.	Placebo tablet orally every evening about one hour before bedtime for one week. Then melatonin 20 mg melatonin orally every evening about 1 hour before bedtime for one week. Three days wash out in between.
Measure Participants	21	23
Mean (Standard Deviation) [units on a scale]	-9.9 (23.4)	-4.6 (30.9)

3. Secondary Outcome

Title	Emotional Function as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006)
Description	Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Emotional function was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated the best possible emotional function. Note outcome reported for complete compliers
Time Frame	One week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Melatonin Then Placebo	Placebo Then Melatonin
Arm/Group Description	20 mg Melatonin orally every evening about 1 hour before bedtime for one week. Then Placebo tablet orally every evening about one hour before bedtime for one week. Three days wash out in between.	Placebo tablet orally every evening about one hour before bedtime for one week. Then melatonin 20 mg melatonin orally every evening about 1 hour before bedtime for one week. Three days wash out in between.
Measure Participants	21	23
Mean (Standard Deviation) [units on a scale]	-0.6 (23.5)	3.3 (18.5)

4. Secondary Outcome

Title	Pain as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006)
Description	Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Pain was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated maximum pain. Note outcome reported for complete compliers
Time Frame	One week

Outcome Measure Data

Analysis Population Description

Complete compliers

Arm/Group Title	Melatonin Then Placebo	Placebo Then Melatonin
Arm/Group Description	20 mg Melatonin orally every evening about 1 hour before bedtime for one week. Then Placebo tablet orally every evening about one hour before bedtime for one week. Three days wash out in between	Placebo tablet orally every evening about one hour before bedtime for one week. Then melatonin 20 mg melatonin orally every evening about 1 hour before bedtime for one week. Three days wash out in between.
Measure Participants	21	23
Mean (Standard Deviation) [units on a scale]	0.8 (19.3)	1.9 (22.2)

5. Secondary Outcome

Title	Quality of Life as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006)
Description	Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Quality of Life was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated best possible quality of life. Note outcome reported for complete compliers
Time Frame	One week

Outcome Measure Data

Analysis Population Description

Complete compliers

Arm/Group Title	Melatonin Then Placebo	Placebo Then Melatonin
Arm/Group Description	20 mg Melatonin orally every evening about 1 hour before bedtime for one week. Then Placebo tablet orally every evening about one hour before bedtime for one week. Three days wash out in between.	Placebo tablet orally every evening about one hour before bedtime for one week. Then melatonin 20 mg melatonin orally every evening about 1 hour before bedtime for one week. Three days wash out in between.
Measure Participants	21	23
Mean (Standard Deviation) [units on a scale]	-0.8 (13.6)	-3.2 (19.2)

6. Secondary Outcome

Title	Appetite Loss as Measured by the Questionnaire EORTC QLQ-C15-PAL (Groenvold M, Petersen MA, Aaronson NK, et al, Eur J Cancer 42:55-64, 2006)
Description	Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). Appetite loss was converted to a 0 til 100 scale according to the scoring manual for EORTC QLQ C15-PAL where 100 indicated maximum appetite loss (worst possible). Note outcome reported for complete compliers
Time Frame	One week

Outcome Measure Data

Analysis Population Description

Complete compliers

Arm/Group Title	Melatonin Then Placebo	Placebo Then Melatonin
Arm/Group Description	20 mg Melatonin orally every evening about 1 hour before bedtime for one week. Then Placebo tablet orally every evening about one hour before bedtime for one week. Three days wash out in between.	Placebo tablet orally every evening about one hour before bedtime for one week. Then melatonin 20 mg melatonin orally every evening about 1 hour before bedtime for one week. Three days wash out in between.
Measure Participants	21	23
Mean (Standard Deviation) [units on a scale]	-0.8 (25.4)	-3.2 (21.6)

7. Secondary Outcome

Title	General Fatigue Measured by the The Multidimensional Fatigue Inventory (MFI)
Description	Change from baseline to week one in intervention group minus change from baseline to week one in control group. Because it was a cross-over trial this was calculated the following way: Outcomes for arm 1 (melatonin then placebo) were calculated as the difference in mean change scores between week 1 and week 2 (scores for day 7 to day 1-scores for day 17 to day 10). Outcomes for arm 2 (placebo then melatonin) were calculated as the difference in mean change scores between week 2 and week 1 (scores for day 17 to day 10-scores for day 7 to day 1). The general fatigue scale that consits of four items was converted to a 0 til 100 scale where 100 indicated maximum (worst possible) fatigue. Note outcome reported for complete compliers
Time Frame	One week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Melatonin Then Placebo	Placebo Then Melatonin
Arm/Group Description	20 mg Melatonin orally every evening about 1 hour before bedtime for one week. Then Placebo tablet orally every evening about one hour before bedtime for one week. Three days wash out in between.	Placebo tablet orally every evening about one hour before bedtime for one week. Then melatonin 20 mg melatonin orally every evening about 1 hour before bedtime for one week. Three days wash out in between.
Measure Participants	21	23
Mean (Standard Deviation) [units on a scale]	-3.2 (18.6)	-2.1 (24.8)

Adverse Events

Time Frame	SUSARS were registered for part 1 (two weeks plus washout phase) and part 2 (six weeks)
Adverse Event Reporting Description	Only SUSAR (suspected unexpected serious adverse reactions) are reported because the study population was patients in palliative care with many potential adverse events Data are not presented per intervention and since there were '0' SUSAR in both groups this does not matter.
Arm/Group Title	Melatonin Then Placebo		Placebo Then Melatonin
Arm/Group Description	Melatonin 20 mg melatonin orally every evening about 1 hour before bedtime for one week. Then placebo for one week.		Placebo tablet orally every evening about one hour before bedtime for one week. Then melatonin 20 mg. for one week.
All Cause Mortality
	Melatonin Then Placebo		Placebo Then Melatonin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Melatonin Then Placebo		Placebo Then Melatonin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	Melatonin Then Placebo		Placebo Then Melatonin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/38 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.