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Not yet recruitingNCT07846865TIRZE-PAPUpdated Sep 29, 2026

Tirzepatide Versus Positive Airway Pressure for the Treatment of Obstructive Sleep Apnoea: A Randomised Comparative Effectiveness Trial

A Phase 2/3 interventional study of Continuous Positive Airway Pressure and Tirzepatide in Sleep Apnoea, Obesity & Overweight and Sleep Apnea Syndrome, Obstructive, sponsored by Woolcock Institute of Medical Research. Not yet recruiting at 1 site in Australia. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by Woolcock Institute of Medical Research · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
256
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

When used, continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea (OSA), a condition that is mainly caused by overweight and obesity. However, CPAP is plagued by poor adherence and high rates of discontinued use leaving most patients undertreated and at risk of serious health complications. This study aims to test whether new effective weight loss pharmacotherapy is superior to CPAP for alleviating OSA and improving health outcomes.

Read the detailed description

The TIRZE-PAP study is a parallel randomised superiority trial comparing weight loss with weekly tirzepatide (15mg or the maximum tolerated dose) versus CPAP, in 256 people with moderate-severe OSA (AHI≥15/hr) and overweight or obesity (BMI: ≥27kg/m2). Participants allocated to CPAP will receive therapy as per usual care by their treating physician. Participants allocated to tirzepatide will undergo a 20-week stepped titration with a monthly increase of dose to a maximum 15mg (or maximum tolerated) by week 20. Outcomes will be collected over two 28-day periods commencing at baseline (pre-intervention weeks -4 to 0) and at follow-up (post-intervention weeks 48 to 52).

02

Conditions studied

  • Sleep Apnoea
  • Obesity & Overweight
  • Sleep Apnea Syndrome, Obstructive

Keywords

  • Continuous Positive Airway Pressure
  • Tirzepatide
  • Sleep Apnoea
  • Clinical Trial
  • weight loss
  • GLP1
  • Mounjaro
  • OSA
  • CPAP
  • comparative effectiveness
  • randomized
  • sleep apnea
  • GIP
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Females and Males aged ≥ 18 years at the time of signing informed consent
  • Moderate-severe OSA defined as an AHI ≥ 15/hr determined from a Type 1 or 2 sleep study conducted within the previous 12 months with a clinician recommendation for CPAP therapy.
  • Moderate overweight or obesity defined as BMI ≥ 27 kg/m2. (Adjusted to BMI ≥ 25 kg/m2 for Asian populations as per WHO guidelines (WHO Expert Consultation (2004))
  • No contraindication to tirzepatide use as per Australian Product Information
  • Home internet access to enable cloud storage of SleepTracker-AI in-home BDI.
  • Fluent English literacy and able to provide informed consent.

Exclusion criteria

Exclusion Criteria:

OSA or other respiratory related criteria:

  • Respiratory failure including obesity hypoventilation syndrome (OHS) or daytime hypercapnia or moderate-severe chronic obstructive pulmonary disease (COPD) with FEV1/FVC ratio\<0.7 and FEV1\<80% predicted (GOLD criteria).
  • Driver occupation with excessive sleepiness (Epworth Sleepiness Scale >=16) or sleepiness-related motor vehicle accident or near accident within 12 months prior to enrolment
  • Current or prior (≤3 months) OSA treatment with mechanical therapy (CPAP, MAS, Positional)
  • >50% respiratory events with Cheyne-Stokes Respiration (CSR) or Central Sleep Apnoea (CSA)
  • Relative or absolute contraindication to CPAP including chronic cranial injury; recurrent pneumothorax; indication for oral-pharyngeal surgery, significant craniofacial abnormalities that may affect breathing, or are unwilling to use CPAP
  • Any previous or planned surgery for OSA or major ear, nose or throat surgery, including tonsillectomy and adenoidectomy that still may affect breathing (NB: Inclusion of a participant with more minor ear, nose or throat surgery (for example, deviated septum) will be at the investigator's discretion)

Glycaemia related criteria:

  • HbA1c ≥ 48 mmol/mol (6.5%) at screening
  • Type 1 or type 2 diabetes mellitus
  • Treatment with glucose-lowering agent(s) within 90 days before screening
  • Treatment with a GLP-1 receptor agonist within 90 days before screening

Obesity related criteria:

  • A self-reported change in body weight >5 kg or >5% within 90 days before baseline
  • Treatment with medication for the indication of obesity within 90 days before baseline and/or currently enrolled in a weight loss program

Other criteria:

  • Pregnancy/breast feeding or planning a pregnancy during the trial period
  • Relative or absolute contraindication to tirzepatide including needle phobia
04

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
256 participants (estimated)

Study arms

  • Active comparator
    Continuous Positive Airway Pressure (CPAP)

    Device: Continuous Positive Airway Pressure

  • Experimental
    Tirzepatide

    Drug: Tirzepatide

Interventions

  • DeviceContinuous Positive Airway Pressure

    Participants allocated to CPAP will be managed by their caring sleep physician as per their normal practice. Participants may also be counselled on losing weight with diet and exercise as per usual practice.

  • DrugTirzepatide

    Patients allocated to weight loss with tirzepatide will be managed by the study dietitian. The tirzepatide formulation is administered subcutaneously once weekly using single-use injection pens. Participants will undergo a 20-week dose escalation phase followed by a dose maintenance phase for the remainder of the 12-month study period.

05

What researchers measure

Primary outcomes

  1. Breathing Disturbance Index (BDI)

    BDI is the primary severity metric of OSA in the trial which is measured by the number of breathing disturbances per hour of sleep. This is measured using contactless mattress-based OSA monitors (SleepTracker-AI) that can automatically and reliably measure true OSA alleviation every night for the entire period of sleep.

    Time frame: The mean BDI measured over 28 nights of monitoring is calculated for baseline (Weeks -4 to 0) and follow-up (Weeks 48 to 52)

Secondary outcomes

  1. Hypoxia - Oxygen Desaturation Index (ODI 3%)

    ODI 3% is calculated as the number of oxygen desaturation events ≥3% per hour as a percentage of time in bed, estimated using at-home oximetry (RingConn Gen 2).

    Time frame: ODI 3% will be determined as a mean of 7-10 nights of data acquired at baseline and a mean of 7-10 nights of data acquired at 12month follow-up.

  2. Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment Short Form 8a Score

    The PROMIS Sleep-Related Impairment Short Form 8a Score is used to assess participant-reported levels of alertness, sleepiness, and tiredness and the functional impairments associated with sleep problems or reduced alertness over the past 7 days.

    Time frame: Collected at Baseline and 3,6,9 and 12 months.

  3. Epworth Sleepiness Scale (ESS)

    Subjective sleepiness scored out of 24 measured using an 8-item questionnaire.

    Time frame: Collected at Baseline and 3,6,9 and 12 months.

  4. Ambulatory Blood Pressure - Sleep Systolic Blood Pressure (SBP)

    Sleep SBP is measured hourly, using an ambulatory blood pressure monitor, for a self-reported sleep period.

    Time frame: Baseline and Week 52

  5. Cardiometabolic Fasted Blood Markers - Low-Density Lipoproteins (LDL)

    Low-density lipoproteins are measured from fasted venous blood.

    Time frame: Screening and Week 52

  6. Cardiometabolic Fasted Blood Markers - HbA1c

    HbA1c, or glycated haemoglobin, assesses long-term glycaemic control. It is measured from fasted venous blood.

    Time frame: Screening and Week 52

Other outcomes

  1. Hypoxic Burden

    This is an oximetry-derived measurement using established algorithms. Hypoxic burden measures are quantified from nightly at-home oximetry acquired using an oximeter device (RingConn Gen 2).

    Time frame: The mean nightly hypoxic burden measured over 7-10 nights of monitoring is calculated for baseline and 12 month follow-up.

  2. Short Form Functional Outcomes of Sleep Questionnaire (FOSQ-10)

    The FOSQ-10 is used to assess the impact of sleep disorders/excessive sleepiness on daily functioning.

    Time frame: Baseline and 3, 6, 9 and 12 months.

  3. Cardiometabolic Fasted Blood Markers - Glucose

    Glucose is measured from fasted venous blood.

    Time frame: Screening and Week 52

  4. Cardiometabolic Fasted Blood Markers - Triglycerides [TAG]

    Triglycerides are measured from fasted venous blood.

    Time frame: Screening and Week 52

  5. Cardiometabolic Fasted Blood Markers - High-Density Lipoproteins (HDL)

    High-density lipoproteins are measured from fasted venous blood.

    Time frame: Screening and Week 52

  6. Cardiometabolic Fasted Blood Markers - Total Cholesterol

    Total cholesterol is measured from fasted venous blood.

    Time frame: Screening and Week 52

  7. Ambulatory Blood Pressure - Sleep Diastolic Blood Pressure (DBP)

    Sleep DBP is measured hourly over 24 hours using an ambulatory blood pressure monitor, segmented for a self-reported sleep period.

    Time frame: Baseline and Week 52

  8. Ambulatory Blood Pressure - Wake Systolic Blood Pressure (SBP)

    Wake SBP is measured hourly over 24 hours using an ambulatory blood pressure monitor, segmented for a self-reported wake period.

    Time frame: Baseline and Week 52

  9. Ambulatory Blood Pressure - Wake Diastolic Blood Pressure (DBP)

    Wake DBP is measured hourly over 24 hours using an ambulatory blood pressure monitor, segmented for a self-reported wake period.

    Time frame: Baseline and Week 52

  10. Ambulatory Blood Pressure - 24-hour Mean Arterial Pressure (MAP)

    24-hour MAP is calculated hourly over 24 hours using an ambulatory blood pressure monitor. MAP = DBP + (SBP - DBP)/3

    Time frame: Baseline and Week 52

  11. Office Blood Pressure - Systolic Blood Pressure (SBP)

    SBP is measured using an automated blood pressure machine after sitting quietly for 5 minutes.

    Time frame: Baseline and Week 52

  12. Office Blood Pressure - Diastolic Blood Pressure (DBP)

    DBP is measured using an automated blood pressure machine after sitting quietly for 5 minutes.

    Time frame: Baseline and Week 52

  13. Anthropometry - Body Mass Index (kg/m^2)

    BMI is calculated as weight in kilograms, divided by height measured in metres squared.

    Time frame: Baseline and Week 52

  14. Anthropometry - Weight (kg)

    Weight is measured in kilograms.

    Time frame: Baseline and Week 52

  15. Anthropometry - Body Weight (% change)

    Change in Weight is calculated as a percentage of change from baseline to 52-weeks.

    Time frame: Baseline and Week 52

  16. Anthropometry - Waist Circumference

    Waist circumference is measured in centimetres, using a tape measure positioned in line with the superior iliac crest of the hip.

    Time frame: Baseline and Week 52

  17. Anthropometry - Neck Circumference

    Neck circumference is measured in centimetres, using a tape measure positioned inferior to the laryngeal prominence.

    Time frame: Baseline and Week 52

  18. CAmbridge Neuropsychological Test Automated Battery (CANTAB) Multitasking Test

    The Multitasking Test is used to assess executive functioning and cued attentional set shifting.

    Time frame: Baseline and Week 52

  19. CANTAB Spatial Working Memory Task

    The Spatial Working Memory Task is used to assess working memory and strategy and is applicable in the assessment of general cognitive function.

    Time frame: Baseline and Week 52

  20. Psychomotor Vigilance Task (PVT)

    The PVT is used to assess a participant's level of alertness.

    Time frame: Baseline and Week 52

  21. Blood-Based Neurodegeneration Biomarkers - Amyloid Beta

    Amyloid Beta, a peptide associated with Alzheimer's disease, is measured from fasted venous blood.

    Time frame: Baseline and Week 52

  22. Blood-Based Neurodegeneration Biomarkers - Phosphorylated Tau

    Phosphorylated Tau \[p-Tau-217\], a tau protein with added phosphate groups, is measured from fasted venous blood.

    Time frame: Baseline and Week 52

  23. Blood-Based Neurodegeneration Biomarkers - Glial Fibrillary Acidic Protein (GFAP)

    GFAP, a structural protein found in astrocytic cells, is measured from fasted venous blood.

    Time frame: Baseline and Week 52

  24. Hypoxia - Time Spent With SpO2<88%

    Time spent with SpO2\<88% is calculated as the time spent with oxygen saturation below 88% as a percentage of time in bed, estimated using at-home oximetry.

    Time frame: Hypoxia outcomes will be determined as a mean of 7-10 nights of data acquired at baseline and a mean of 7-10 nights of data acquired at 12months.

  25. Hypoxia - Minimum SpO2

    Minimum SpO2 is calculated as the minimum oxygen saturation reached during time in bed, estimated using at-home oximetry.

    Time frame: Hypoxia outcomes will be determined as a mean of 7-10 nights of data acquired at baseline and a mean of 7-10 nights of data acquired at 12 month follow-up

  26. Hypoxia - Average Desaturation

    Average desaturation is calculated as the mean of all desaturation events \>=3% during time in bed, estimated using at-home oximetry.

    Time frame: Hypoxia outcomes will be determined as a mean of 7-10 nights of data acquired at baseline and a mean of 7-10 nights of data acquired at 12 month follow-up

  27. Breathing Disturbance Index (BDI)

    BDI is measured by the number of breathing disturbances per hour of sleep using contactless mattress-based OSA monitors (SleepTracker-AI).

    Time frame: Nightly for 12-month treatment duration.

  28. Anthropometry - Weight (Self-Measured)

    Weight (kg) - self-measured at home

    Time frame: At Baseline, 3, 6, and 9 months

06

Study locations

1 site
  • Woolcock Institute of Medical Research
    Macquarie Park, New South Wales 2113, Australia
07

References and documents

Individual participant data

Plan to share: Yes — Non-identifiable IPD will be shared upon reasonable request to the Principal Investigators.

Supporting information: Study protocol, Sap, Icf, Csr, Analytic code

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07846865
Lead sponsor
Woolcock Institute of Medical Research
Responsible party
Craig Phillips (Associate Professor, Woolcock Institute of Medical Research) — Principal investigator
First posted
Sep 29, 2026
Start date
Oct 1, 2026 (estimated)
Primary completion
Dec 1, 2028 (estimated)
Completion
Dec 1, 2028 (estimated)
Last update
Sep 29, 2026

Study contacts

Craig Phillips, PhD
Contact
c.phillips@mq.edu.au
02 9805 3000
Julia Chapman, PhD
Contact
julia.chapman@woolcock.org.au
Craig Phillips
principal investigator · Woolcock Institute of Medical Research and Macquarie Medical School, Macquarie University, Sydney, NSW, Australia
Ron Grunstein
principal investigator · Woolcock Institute of Medical Research and Macquarie Medical School, Macquarie University, Sydney, NSW, Australia
Camilla Hoyos, PhD
study chair · Woolcock Institute of Medical Research

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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