Home » Trials » SLCTR/2018/007


Efficacy and safety of once weekly thyroxine versus daily thyroxine as maintenance therapy of hypothyroidism; a randomized controlled exploratory clinical trial -

SLCTR Registration Number

SLCTR/2018/007


Date of Registration

09 Feb 2018

The date of last modification

Feb 09, 2018



Application Summary


Scientific Title of Trial

Efficacy and safety of once weekly thyroxine versus daily thyroxine as maintenance therapy of hypothyroidism; a randomized controlled exploratory clinical trial


Public Title of Trial

Efficacy and safety of once weekly thyroxine versus daily thyroxine as maintenance therapy of hypothyroidism; a randomized controlled exploratory clinical trial


Disease of Health Condition(s) Studied

Hypothyroidism


Scientific Acronym

None


Public Acronym

None


Brief title

None


Universal Trail Number

U1111-1202-3740


Any other number(s) assigned to the trial and issuing authority

67/17 (ERC: Sri Jayewardenepura)


Trial Details


What is the research question being addressed?

What is the efficacy, safety and acceptability of once weekly dosing of thyroxine compared to daily dosing of thyroxine as maintenance therapy for hypothyroidism?


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Single blinded


Control

Standard therapy


Assignment

Parallel


Purpose

Treatment


Intervention(s) planned

Study setting: Endocrine clinic, Colombo South Teaching Hospital, Sri Lanka

Method of allocation: Simple randomization using a pre-planned computer generated random table. Random table will be kept with an investigator not involved in patient recruitment and randomization of each patient will be done via telephone to maintain allocation concealment.

Intervention group: participants will receive oral thyroxine once weekly in a dose 7 times the individual’s usual daily maintenance dose beginning on day 1 of the trial, with no thyroxine given on days in between. Duration of treatment : 12 weeks

Control group: participants will continue to take thyroxine daily in the individual’s usual daily maintenance dose. Trial medications will be provided to the patients by the investigators and all trial patients will receive the same brand of thyroxine. Duration of treatment : 12 weeks

Participants and healthcare providers will not be blinded; Outcome assessors and data analysts will be blinded to the intervention status of the participants.


Inclusion criteria

  1. Age >18 years and <70 years
  2. Primary hypothyroidism due to autoimmune hypothyroidism, thyroidectomy or radioiodine treatment
  3. Serum Thyroid-Stimulating Hormone (TSH) and free thyroxine (T4) are within normal range
  4. No change in thyroxine dose in the past 3 months
  5. Baseline blood pressure <140/90 mmHg
  6. Baseline pulse rate <90 bpm
  7. Adequate contraceptive measures for women of childbearing age
  8. Meaningful consent is available

Exclusion criteria

  1. Ischaemic heart disease (previous acute coronary syndrome, stable angina, coronary artery revascularization or evidence of cardiac ischaemia on ECG, exercise ECG or echocardiography)
  2. Pre-existing heart failure or ejection fraction <50% on echocardiography
  3. History of cardiac arrhythmia
  4. Uncontrolled hypertension (BP >140/90 mmHg)
  5. Renal failure with eGFR <45 ml/min/1.73m2
  6. Pre-existing chronic liver disease or liver transaminases >5 times upper limit of normal reference range
  7. Bone fracture in past 3 months
  8. Paget’s disease of bone
  9. Malabsorption
  10. Pregnancy
  11. History of thyroid malignancy
  12. Any terminal disease (eg. advanced heart failure, advanced respiratory disease, malignancy)
  13. Not available for follow-up (e.g. no fixed address, unable to come for regular clinic follow-ups)
  14. Participation in another clinical trial within 3 months


Primary outcome(s)

  1. Proportion of patients maintained in euthyroid state
  2. Mean TSH and free T4
  3. Mean end-systolic diameter, end diastolic diameter and ejection fraction on echocardiogram
  4. Mean Hyperthyroid Symptom Score (Klein et al, 1988)

Primary outcome(s) - Time of assessment(s)

  1. End of the study period of 12 weeks

  2. At the end of the study period of 12 weeks

  3. 4 – 6 hours after first dose of thyroxine and 12 weeks after being on the prescribed regimen.

  4. 4 - 6 hours after first dose of thyroxine and 12 weeks after being on the prescribed regimen


Secondary outcome

  1. Mean blood pressure
  2. Mean heart rate
  3. Incidence of cardiac complications (composite of tachyarrhythmias, stable angina, acute coronary syndromes, heart failure)
  4. Incidence of biochemically confirmed thyrotoxicosis
  5. Mean visual analogue Arizona Integrative Outcomes Scale (AIOS) score to assess patient well-being

Secondary outcome(s) - Time of assessment(s)

  1. Mean blood pressure
  2. Mean heart rate
  3. Incidence of cardiac complications (composite of tachyarrhythmias, stable angina, acute coronary syndromes, heart failure)
  4. Incidence of biochemically confirmed thyrotoxicosis
  5. Mean visual analogue Arizona Integrative Outcomes Scale (AIOS) score to assess patient well-being


Target number/sample size

100 (50 in each arm)


Countries of recruitment

Sri Lanka


Anticipated start date

2018-05-01


Anticipated end date

2020-01-01


Recruitment status

Pending


State of ethics review approval

Approved by the Ethical Review Committee of Faculty of Medical Sciences, University of Sri Jayawardenepura on 27th November 2017 (Ref. 67/17)


Funding source

None (Investigator funded)



Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Dr. D.U.S Bulugahapitiya
Consultant Endocrinologist
Diabetes and Endocrine Unit, Colombo South Teaching Hospital, Kalubowila, Sri Lanka.

Mob: 0777356105

udithakaush@googlemail.com

Contact Person for Public Queries

Dr. D.U.S Bulugahapitiya
Consultant Endocrinologist
Diabetes and Endocrine Unit, Colombo South Teaching Hospital, Kalubowila, Sri Lanka.

Mob: 0777356105

udithakaush@googlemail.com


Primary study sponsor/organization

Dr. D.U.S Bulugahapitiya
Consultant Endocrinologist
Diabetes and Endocrine Unit, Colombo South Teaching Hospital, Kalubowila, Sri Lanka.
Mob: 0777356105

udithakaush@googlemail.com

Secondary study sponsor (If any)

None