Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 1521422 | Other Grant/Funding Number | Central Arkansas Veterans Healthcare System |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Central Arkansas Veterans Healthcare System | FED |
Not provided
Not provided
Not provided
The investigators propose the following hypothesis: discontinuation of levothyroxine (LT4) for veterans with subclinical hypothyroidism (SCH) will be feasible, acceptable, and safe and will not negatively affect their Quality of Life (QoL). The investigators aim to evaluate the feasibility of LT4 discontinuation among veterans with SCH and determine the changes in QoL measures, lipids, and adverse events.
This is a pilot, randomized, double-blind, placebo-controlled trial.
Methodology:
The investigators will conduct a double-blind, placebo-controlled clinical trial where eligible veterans diagnosed with SCH and on LT4 will be 1:1 randomized to either continue LT4 or change to placebo. The primary outcome is intervention feasibility (willingness to enter the trial, recruitment rate, and completion rate). Secondary outcomes are: 1) changes in QoL measures (Hypothyroid Symptom [HSS] and Tiredness scale scores of the Thyroid-Specific Patient-Related Outcome Measure [ThyPRO], EuroQoL 5-Dimension Self-Report Questionnaire) measured at baseline, 6-8 weeks and 6 months and 2) changes in lipids assessed at baseline and 6 months, and 3) incidence of adverse events (overt hypothyroidism, hyperthyroidism, atrial fibrillation, fractures, acute myocardial infarction, stroke, acute coronary syndrome, heart failure, mortality).
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Levothyroxine group ("sham discontinuation") | Active Comparator | Continue the current dose of levothyroxine. The brand of levothyroxine to be used in this study will be Synthroid tablets of 25 mcg, 50 mcg, and 75 mcg (AbbVie Inc). |
|
| Placebo group ("real discontinuation") | Placebo Comparator | Stop the current dose of levothyroxine and take study placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Levothyroxine | Drug | Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Participants' Willingness to Enter the Trial | Percent of eligible participants approached who consented to participate during the recruitment phase. | The time from first consent signed to last consent signed. March 2021 to April 2022. |
| Recruitment Rate | The number of enrolled (consented) participants divided by the length of the recruitment period. | The time from first consent signed to last consent signed. March 2021 to April 2022. 13 months. |
| Completion Rate | Percentage of randomized participants who completed the trial. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) - Hypothyroid Symptoms Score | The Hypothyroid Symptoms score from the Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire is assessed on a scale from 0 to 100, with higher scores indicating more symptoms. | Baseline, 6 weeks and 6 months |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Spyridoula Maraka, MD MS | Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR | North Little Rock | Arkansas | 72114-1706 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34152370 | Background | Brito JP, Ross JS, El Kawkgi OM, Maraka S, Deng Y, Shah ND, Lipska KJ. Levothyroxine Use in the United States, 2008-2018. JAMA Intern Med. 2021 Oct 1;181(10):1402-1405. doi: 10.1001/jamainternmed.2021.2686. | |
| 30285179 | Background | Feller M, Snel M, Moutzouri E, Bauer DC, de Montmollin M, Aujesky D, Ford I, Gussekloo J, Kearney PM, Mooijaart S, Quinn T, Stott D, Westendorp R, Rodondi N, Dekkers OM. Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related Symptoms in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis. JAMA. 2018 Oct 2;320(13):1349-1359. doi: 10.1001/jama.2018.13770. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Of 52 enrolled participants, 50 were randomized to treatment.
Participants were recruited based on opt-in/opt-out letter at 1 VA medical center between March 2021 and April 2022. The first participant was enrolled on March 24, 2021 and the last participant was enrolled in April 2022.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Levothyroxine Group ("Sham Discontinuation") | Continue the current dose of levothyroxine. The brand of levothyroxine to be used in this study will be Synthroid tablets of 25 mcg, 50 mcg, and 75 mcg (AbbVie Inc). Levothyroxine: Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day. |
| FG001 | Placebo Group ("Real Discontinuation") | Stop the current dose of levothyroxine and take study placebo Placebo: Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Levothyroxine Group ("Sham Discontinuation") | Continue the current dose of levothyroxine. The brand of levothyroxine to be used in this study will be Synthroid tablets of 25 mcg, 50 mcg, and 75 mcg (AbbVie Inc). Levothyroxine: Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Participants' Willingness to Enter the Trial | Percent of eligible participants approached who consented to participate during the recruitment phase. | The number of patients consented divided by the total number of eligible patients contacted. | Posted | Count of Participants | Participants | The time from first consent signed to last consent signed. March 2021 to April 2022. |
|
|
6 months
Of the 50 randomized participants, 24 were assigned to the LT4 group and 26 were assigned to the placebo group. There were 5 post-randomization exclusions, resulting in 21 participants in the LT4 group and 24 participants in the placebo group. One participant in the placebo group was discontinued (participant choice) prior to Week 6. This resulted in 21 participants in the LT4 group and 23 participants in the placebo group for the final analysis cohort.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Levothyroxine Group ("Sham Discontinuation") | Continue the current dose of levothyroxine. The brand of levothyroxine to be used in this study will be Synthroid tablets of 25 mcg, 50 mcg, and 75 mcg (AbbVie Inc). Levothyroxine: Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gangrene of toe | Skin and subcutaneous tissue disorders | SNOMED CT | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| fracture of rib | Injury, poisoning and procedural complications | SNOMED CT | Systematic Assessment | Fractures |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Spyridoula Maraka, MD, MS | Central Arkansas Veterans Healthcare System | (501) 257-5848 | Spyridoula.Maraka@va.gov |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 30, 2023 | Sep 25, 2023 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 1, 2021 | Jun 22, 2022 | ICF_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D013974 | Thyroxine |
| ID | Term |
|---|---|
| D013963 | Thyroid Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D024322 | Amino Acids, Aromatic |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo | Other | Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day. |
|
| Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) - Tiredness Score |
The Tiredness score from the Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire is assessed on a scale from 0 to 100, with higher scores indicating more tiredness. |
| Baseline, 6 weeks and 6 months |
| Euro Quality of Life 5-Dimension Self-Report Questionnaire (EQ-5D) Score at Week 6 and Month 6 | The EuroQoL [EQ] Group 5-Dimension Self-Report Questionnaire (EQ-5D) scores include the EQ-5D descriptive index, on a scale from -0.59 to 1.00. Higher scores indicate better quality of life. The EQ-5D scores include the score on the EQ visual-analogue scale (EQ-5D VAS), on a scale from 0 to 100. Higher scores indicate better quality of life. | 6 weeks and 6 months |
| Lipid Levels | Differences in mean 6-month lipid levels after adjusting for gender and baseline lipid level. | 6 months |
| 28402245 | Background | Stott DJ, Rodondi N, Kearney PM, Ford I, Westendorp RGJ, Mooijaart SP, Sattar N, Aubert CE, Aujesky D, Bauer DC, Baumgartner C, Blum MR, Browne JP, Byrne S, Collet TH, Dekkers OM, den Elzen WPJ, Du Puy RS, Ellis G, Feller M, Floriani C, Hendry K, Hurley C, Jukema JW, Kean S, Kelly M, Krebs D, Langhorne P, McCarthy G, McCarthy V, McConnachie A, McDade M, Messow M, O'Flynn A, O'Riordan D, Poortvliet RKE, Quinn TJ, Russell A, Sinnott C, Smit JWA, Van Dorland HA, Walsh KA, Walsh EK, Watt T, Wilson R, Gussekloo J; TRUST Study Group. Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism. N Engl J Med. 2017 Jun 29;376(26):2534-2544. doi: 10.1056/NEJMoa1603825. Epub 2017 Apr 3. |
| 31088853 | Background | Bekkering GE, Agoritsas T, Lytvyn L, Heen AF, Feller M, Moutzouri E, Abdulazeem H, Aertgeerts B, Beecher D, Brito JP, Farhoumand PD, Singh Ospina N, Rodondi N, van Driel M, Wallace E, Snel M, Okwen PM, Siemieniuk R, Vandvik PO, Kuijpers T, Vermandere M. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ. 2019 May 14;365:l2006. doi: 10.1136/bmj.l2006. |
| 37656124 | Background | Ayala IN, Soto Jacome C, Toro-Tobon D, Golembiewski E, Garcia-Bautista A, Hidalgo J, Cordova-Madera S, Al Anbari R, Sohn R J, Singh Ospina N, Maraka S, Joseph M, Brito JP. Appropriateness of Levothyroxine Prescription: A Multicenter Retrospective Study. J Clin Endocrinol Metab. 2024 Jan 18;109(2):e765-e772. doi: 10.1210/clinem/dgad517. |
| 37279296 | Background | Toloza FJK, El Kawkgi OM, Spencer HJ, Mathews SE, Garcia A, Gamboa A, Mirza N, Mohan S, Vallejo S, Bogojevic M, Rodriguez-Gutierrez R, Singh Ospina NM, Brito JP, Maraka S. Determinants for Thyroid Hormone Replacement Therapy in Subclinical Hypothyroidism: A Multicenter Electronic Health Records-Based Study. Thyroid. 2023 Sep;33(9):1045-1054. doi: 10.1089/thy.2023.0062. Epub 2023 Jun 26. |
| 33977312 | Background | Ospina NS, Salloum RG, Maraka S, Brito JP. De-implementing low-value care in endocrinology. Endocrine. 2021 Aug;73(2):292-300. doi: 10.1007/s12020-021-02732-y. Epub 2021 May 11. |
| 33161885 | Background | Burgos N, Toloza FJK, Singh Ospina NM, Brito JP, Salloum RG, Hassett LC, Maraka S. Clinical Outcomes After Discontinuation of Thyroid Hormone Replacement: A Systematic Review and Meta-Analysis. Thyroid. 2021 May;31(5):740-751. doi: 10.1089/thy.2020.0679. Epub 2020 Dec 29. |
| 40736623 | Derived | Maraka S, Owen RR, Singh Ospina NM, Knox M, Dodds T, Thostenson JD, Dishongh K, Raciborski RA, Albashaireh A, Shah A, Syed S, Naqvi S, Motahari H, Thumma S, Toloza F, Ambrogini E, Brito JP. Discontinuation of levothyroxine therapy in patients with subclinical hypothyroidism: a pilot randomized clinical trial. Endocrine. 2025 Nov;90(2):781-792. doi: 10.1007/s12020-025-04371-z. Epub 2025 Jul 30. |
| BG001 | Placebo Group ("Real Discontinuation") | Stop the current dose of levothyroxine and take study placebo Placebo: Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | pounds |
|
| Body mass index | Mean | Standard Deviation | kg/m^2 |
|
| Systolic Blood Pressure (SBP) | Mean | Standard Deviation | mm Hg |
|
| Diastolic Blood Pressure (DBP) | Mean | Standard Deviation | mm Hg |
|
| Pulse | Mean | Standard Deviation | beats/min |
|
| Total Cholesterol | Mean | Standard Deviation | mg/dL |
|
| LDL | Mean | Standard Deviation | mg/dL |
|
| HDL | Mean | Standard Deviation | mg/dL |
|
| Triglycerides | Mean | Standard Deviation | mg/dL |
|
| Levothyroxine (LT4) dose prior to enrollment, 25mcg | Count of Participants | Participants |
|
| LT4 dose prior to enrollment, 50mcg | Count of Participants | Participants |
|
| LT4 dose prior to enrollment, 75mcg | Count of Participants | Participants |
|
| LT4 duration, < 2 yrs | Count of Participants | Participants |
|
| LT4 duration, 2 to 7 yrs | Count of Participants | Participants |
|
| LT4 duration, > 7 yrs | Count of Participants | Participants |
|
| thyroid-stimulating hormone (TSH) | Mean | Standard Deviation | mIU/L |
|
| free thyroxine (FT4) | Mean | Standard Deviation | ng/dL |
|
| thyroid peroxidase (TPO) positivity | Count of Participants | Participants |
|
| Hypothyroid Symptoms score | The Hypothyroid Symptoms score from the Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire is assessed on a scale from 0 to 100, with higher scores indicating more symptoms. The minimum clinically important difference has been estimated as 9 points. | Mean | Standard Deviation | scores on scale |
|
| Tiredness score | The Tiredness score from the Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire is assessed on a scale from 0 to 100, with higher scores indicating more tiredness. The minimum clinically important difference has been estimated as 9 points. | Mean | Standard Deviation | scores on scale |
|
| ThyPRO-39 score | ThyPRO-39 scales range 0-100, with higher levels corresponding to more symptoms or more quality of life impairment. | Mean | Standard Deviation | scores on scale |
|
| EQ-5D Descriptive score | The EuroQoL [EQ] Group 5-Dimension Self-Report Questionnaire (EQ-5D) scores include the EQ-5D descriptive index, on a scale from -0.59 to 1.00. Higher scores indicate better quality of life. | Mean | Standard Deviation | scores on scale |
|
| EQ-5D VAS score | The EuroQoL [EQ] Group 5-Dimension Self-Report Questionnaire (EQ-5D) scores include the score on the EQ visual-analogue scale (EQ-5D VAS), on a scale from 0 to 100. Higher scores indicate better quality of life. | Mean | Standard Deviation | scores on scale |
|
| Participants |
|
|
| Primary | Recruitment Rate | The number of enrolled (consented) participants divided by the length of the recruitment period. | The number of participants enrolled divided by the length of recruitment period (13 months). | Posted | Number | participants per month | The time from first consent signed to last consent signed. March 2021 to April 2022. 13 months. |
|
|
|
| Primary | Completion Rate | Percentage of randomized participants who completed the trial. | Number of randomized participants that completed the trial divided by the total number of randomized participants. | Posted | Count of Participants | Participants | 6 months |
|
|
|
| Secondary | Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) - Hypothyroid Symptoms Score | The Hypothyroid Symptoms score from the Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire is assessed on a scale from 0 to 100, with higher scores indicating more symptoms. | All randomized participants who completed 6 months follow-up visit. An intent-to-treat strategy was employed where participants were analyzed in the group to which they were randomized, regardless of protocol deviations. | Posted | Mean | Standard Deviation | score on a scale | Baseline, 6 weeks and 6 months |
|
|
|
|
| Secondary | Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) - Tiredness Score | The Tiredness score from the Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire is assessed on a scale from 0 to 100, with higher scores indicating more tiredness. | All randomized participants who completed 6 months follow-up visit. An intent-to-treat strategy was employed where participants were analyzed in the group to which they were randomized, regardless of protocol deviations. | Posted | Mean | Standard Deviation | score on a scale | Baseline, 6 weeks and 6 months |
|
|
|
|
| Secondary | Euro Quality of Life 5-Dimension Self-Report Questionnaire (EQ-5D) Score at Week 6 and Month 6 | The EuroQoL [EQ] Group 5-Dimension Self-Report Questionnaire (EQ-5D) scores include the EQ-5D descriptive index, on a scale from -0.59 to 1.00. Higher scores indicate better quality of life. The EQ-5D scores include the score on the EQ visual-analogue scale (EQ-5D VAS), on a scale from 0 to 100. Higher scores indicate better quality of life. | All randomized participants who completed 6 months follow-up visit. An intent-to-treat strategy was employed where participants were analyzed into the group they were randomized, regardless of protocol deviations. | Posted | Mean | Standard Deviation | score on a scale | 6 weeks and 6 months |
|
|
|
|
| Secondary | Lipid Levels | Differences in mean 6-month lipid levels after adjusting for gender and baseline lipid level. | All participants who completed 6-8 weeks and 6 months follow-up visit. | Posted | Mean | Standard Deviation | mg/dL | 6 months |
|
|
|
|
| 0 |
| 21 |
| 3 |
| 21 |
| 9 |
| 21 |
| EG001 | Placebo Group ("Real Discontinuation") | Stop the current dose of levothyroxine and take study placebo Placebo: Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day. | 0 | 23 | 1 | 23 | 15 | 23 |
| catheter ablation of arrhythmogenic focus | Cardiac disorders | SNOMED CT | Systematic Assessment |
|
| revision posterior decompression cervical cord and fusion | Surgical and medical procedures | SNOMED CT | Systematic Assessment |
|
| transurethral prostatectomy | Surgical and medical procedures | SNOMED CT | Systematic Assessment |
|
| metastatic adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | SNOMED CT | Systematic Assessment |
|
| fluoroscopy guided percutaneous insertion of drug eluting stent into coronary artery with contrast | Surgical and medical procedures | SNOMED CT | Systematic Assessment |
|
|
| angina pectoris | Cardiac disorders | SNOMED CT | Systematic Assessment |
|
| diarrhea | Gastrointestinal disorders | SNOMED CT | Systematic Assessment |
|
| fall | Injury, poisoning and procedural complications | SNOMED CT | Systematic Assessment |
|
| cardiac pacemaker replaced | Cardiac disorders | SNOMED CT | Systematic Assessment |
|
| cellulitis | Infections and infestations | SNOMED CT | Systematic Assessment |
|
| COVID-19 | Infections and infestations | SNOMED CT | Systematic Assessment |
|
| cut of foot | Skin and subcutaneous tissue disorders | SNOMED CT | Systematic Assessment |
|
| cut of hand | Skin and subcutaneous tissue disorders | SNOMED CT | Systematic Assessment |
|
| dehydration | Metabolism and nutrition disorders | SNOMED CT | Systematic Assessment |
|
| dental restoration | Surgical and medical procedures | SNOMED CT | Systematic Assessment |
|
| dizziness | Nervous system disorders | SNOMED CT | Systematic Assessment |
|
| dry eye | Eye disorders | SNOMED CT | Systematic Assessment |
|
| fatigue | General disorders | SNOMED CT | Systematic Assessment |
|
| fluttering heart | Cardiac disorders | SNOMED CT | Systematic Assessment |
|
| fracture of phalanx of foot | Injury, poisoning and procedural complications | SNOMED CT | Systematic Assessment |
|
| headache | Nervous system disorders | SNOMED CT | Systematic Assessment |
|
| hernia repair | Surgical and medical procedures | SNOMED CT | Systematic Assessment |
|
| feels hot | Vascular disorders | SNOMED CT | Systematic Assessment |
|
| menopausal flushing | Vascular disorders | SNOMED CT | Systematic Assessment |
|
| hypertensive disorder | Vascular disorders | SNOMED CT | Systematic Assessment |
|
| bronchitis | Infections and infestations | SNOMED CT | Systematic Assessment |
|
| injection of knee | Musculoskeletal and connective tissue disorders | SNOMED CT | Systematic Assessment |
|
| injury of lower leg | Injury, poisoning and procedural complications | SNOMED CT | Systematic Assessment |
|
| intravitreal injection of anti-vascular endothelial growth factor | Eye disorders | SNOMED CT | Systematic Assessment |
|
| kidney stone | Renal and urinary disorders | SNOMED CT | Systematic Assessment |
|
| labored breathing | Respiratory, thoracic and mediastinal disorders | SNOMED CT | Systematic Assessment |
|
| low blood pressure | Vascular disorders | SNOMED CT | Systematic Assessment |
|
| nausea | Gastrointestinal disorders | SNOMED CT | Systematic Assessment |
|
| carcinoma of prostate | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | SNOMED CT | Systematic Assessment |
|
| numbness of hand | Nervous system disorders | SNOMED CT | Systematic Assessment |
|
| open wound of buttock | Infections and infestations | SNOMED CT | Systematic Assessment |
|
| open wound of hip region | Infections and infestations | SNOMED CT | Systematic Assessment |
|
| injury of elbow | Injury, poisoning and procedural complications | SNOMED CT | Systematic Assessment |
|
| pain in coccyx | Injury, poisoning and procedural complications | SNOMED CT | Systematic Assessment |
|
| paresthesia of upper limb | Nervous system disorders | SNOMED CT | Systematic Assessment |
|
| removal of sebaceous cyst | Skin and subcutaneous tissue disorders | SNOMED CT | Systematic Assessment |
|
| restenosis | Cardiac disorders | SNOMED CT | Systematic Assessment |
|
| scalp itchy | Skin and subcutaneous tissue disorders | SNOMED CT | Systematic Assessment |
|
| shoulder pain | Injury, poisoning and procedural complications | SNOMED CT | Systematic Assessment |
|
| simple extraction of tooth | Surgical and medical procedures | SNOMED CT | Systematic Assessment |
|
| spasm | Nervous system disorders | SNOMED CT | Systematic Assessment |
|
| vomiting | Gastrointestinal disorders | SNOMED CT | Systematic Assessment |
|
| lightheadedness | General disorders | SNOMED CT | Systematic Assessment |
|
| multiple joint pain | Musculoskeletal and connective tissue disorders | SNOMED CT | Systematic Assessment |
|
| fall on ice | Injury, poisoning and procedural complications | SNOMED CT | Systematic Assessment |
|
| fractured dental restoration | Injury, poisoning and procedural complications | SNOMED CT | Systematic Assessment |
|
| fixed prosthodontic procedure | Surgical and medical procedures | SNOMED CT | Systematic Assessment |
|
| polyp of sigmoid colon | Gastrointestinal disorders | SNOMED CT | Systematic Assessment |
|
| polyp of transverse colon | Gastrointestinal disorders | SNOMED CT | Systematic Assessment |
|
Not provided
Not provided
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| 6 months |
|
An one-sided α-level of 0.05 will be used to determine the statistical significance of the non-inferiority test. |
| Analysis of 6-week outcome | ANCOVA | A p-value < 0.05 indicates the real discontinuation mean and the sham discontinuation mean are different. Adjusted for gender and baseline HSSs. | 0.8793 | Testing whether group means are different. | Difference in Group Means | 0.8 | 2-Sided | 95 | -9.4 | 10.9 | Differences reported as the sham discontinuation mean minus the real discontinuation mean. These differences have been adjusted for gender and baseline hypothyroid symptom scores. | Other | A two-sided α-level of 0.05 will be used to determine the statistical difference. |
| Analysis of 6-month outcome | ANCOVA | A p-value < 0.05 indicates real discontinuation mean and sham discontinuation mean are different. Analyses adjusted for gender and baseline HSS. | 0.6860 | Group differences. | Difference in Group Means | -2.3 | 2-Sided | 95 | -14.0 | 9.3 | Differences are reported as sham discontinuation mean minus real discontinuation mean. These differences have been adjusted for gender and baseline hypothyroid symptom scores. | Other | A two-sided α-level of 0.05 will be used to determine the statistical significance. |
| 6 months |
|
A one-sided α-level of 0.05 will be used to determine the statistical significance of the non-inferiority test. |
| Analysis of 6-week outcome | ANCOVA | A p-value < 0.05 indicates real discontinuation mean and sham discontinuation mean are different. Analyses adjusted for gender and baseline score. | 0.7104 | Testing whether group means are different. | Difference in Group Means | 2.3 | 2-Sided | 95 | -10.1 | 14.7 | Differences reported as the sham discontinuation mean minus the real discontinuation mean. These mean differences have been adjusted for gender and baseline tiredness score. | Other | A two-sided α-level of 0.05 will be used to determine the statistical significance. |
| Analysis of 6-month outcome | ANCOVA | A p-value < 0.05 indicates real discontinuation mean and sham discontinuation mean are different. Analyses adjusted for gender and baseline score. | 0.3381 | Group differences. | Difference in Group Means | 5.4 | 2-Sided | 95 | -5.9 | 16.7 | Differences reported as sham discontinuation mean minus real discontinuation mean. These differences have been adjusted for gender and baseline tiredness scores. | Other | A two-sided α-level of 0.05 will be used to determine statistical significance. |
| EQ-5D VAS 6 weeks |
|
| EQ-5D VAS 6 months |
|
A two-sided α-level of 0.05 will be used to determine the statistical significance. |
| Analysis of 6-month EQ-5D Descriptive score outcome. | ANCOVA | A p-value < 0.05 indicates real discontinuation mean and sham discontinuation mean are different. Analyses adjusted for gender and baseline score. | 0.9585 | Testing whether group means are different. | Difference in Group Means | 0.003 | 2-Sided | 95 | -0.102 | 0.107 | Differences reported as the sham discontinuation mean minus the real discontinuation mean. These differences have been adjusted for gender and baseline EQ-5D Descriptive scores. | Other | A two-sided α-level of 0.05 will be used to determine the statistical significance. |
| Analysis of 6-week EQ-5D VAS score outcome. | ANCOVA | A p-value < 0.05 indicates real discontinuation mean and sham discontinuation mean are different. Analyses adjusted for gender and baseline score. | 0.0643 | Testing whether group means are different. | Difference in Group Means | 7.0 | 2-Sided | 95 | -0.4 | 14.4 | Differences reported as the sham discontinuation mean minus the real discontinuation mean. These differences have been adjusted for gender and baseline EQ-5D VAS scores. | Other | A two-sided α-level of 0.05 will be used to determine the statistical significance. |
| Analysis of 6-month EQ-5D VAS score outcome. | ANCOVA | A p-value < 0.05 indicates real discontinuation mean and sham discontinuation mean are different. Analyses adjusted for gender and baseline scores. | 0.1742 | Testing whether group means are different. | Difference in Group Means | -6.2 | 2-Sided | 95 | -15.3 | 2.9 | Differences reported as the sham discontinuation mean minus the real discontinuation mean. These differences have been adjusted for gender and baseline EQ-5D VAS scores. | Other | A two-sided α-level of 0.05 will be used to determine the statistical significance. |
| HDL 6 months |
|
| Triglycerides 6 months |
|
A two-sided α-level of 0.05 will be used to determine the statistical significance. |
| Analysis of 6-month LDL outcome. | ANCOVA | A p-value < 0.05 indicates real discontinuation mean and sham discontinuation mean are different. Analyses adjusted for gender and baseline value. | 0.3805 | Testing whether group means are different. | Difference in Group Means | -6.8 | 2-Sided | 95 | -22.2 | 8.6 | Differences reported as the sham discontinuation mean minus the real discontinuation mean. These differences have been adjusted for gender and baseline LDL values. | Other | A two-sided α-level of 0.05 will be used to determine the statistical significance. |
| Analysis of 6-month HDL outcome. | ANCOVA | A p-value < 0.05 indicates real discontinuation mean and sham discontinuation mean are different. Analyses adjusted for gender and baseline value. | 0.5724 | Testing whether group means are different. | Difference in Group Means | 1.7 | 2-Sided | 95 | -4.44 | 7.9 | Differences reported as the sham discontinuation mean minus the real discontinuation mean. These differences have been adjusted for gender and baseline HDL values. | Other | A two-sided α-level of 0.05 will be used to determine the statistical significance. |
| Analysis of 6-month triglyceride outcome. | ANCOVA | A p-value < 0.05 indicates real discontinuation mean and sham discontinuation mean are different. Analyses adjusted for gender and baseline value. | 0.3939 | Testing whether group means are different. | Difference in Group Means | -17.8 | 2-Sided | 95 | -59.4 | 23.9 | Differences reported as the sham discontinuation mean minus the real discontinuation mean. These differences have been adjusted for gender and baseline triglyceride values. | Other | A two-sided α-level of 0.05 will be used to determine the statistical significance. |