TTR Cardiac AmyloidosisPhase 3NCT03481972
A Study of Doxycycline and Tauroursodeoxycholic Acid (Doxy/TUDCA) Plus Standard Supportive Therapy Versus Standard Supportive Therapy Alone in Cardiac Amyloidosis Caused by Transthyretin
A Phase 3 study testing Doxycycline and tauroursodeoxycholic acid in people with TTR Cardiac Amyloidosis, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 1 site in Italy.
Trial summary
Cardiac amyloidosis caused by transthyretin either mutated (in ATTRm amyloidosis) or wildtype (in ATTRwt, formerly senile, amyloidosis) is a rare disease but is diagnosed with increasing frequency thanks to the availability of non-invasive scintigraphy-based means. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- TTR Cardiac Amyloidosis
- What is being tested?
- Doxycycline and tauroursodeoxycholic acid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 1 siteItaly
- Study dates
- 11 Apr 2018to 22 Jun 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must meet all of the following criteria:
- Diagnosis of ATTRwt amyloidosis, or ATTRm p.Ile68Leu and p.Val122Ile;
- the diagnosis of amyloidosis needs to be biopsy-proven, and amyloid deposits need to be characterized as ATTR-type by immuno-electron microscopy or mass spectrometry. Biopsy can be omitted in patients with a positive (score 3) cardiac 99mTc-DPD scintigraphy, provided serum and urine immunofixation does not show monoclonal components. Wild-type and mutated ATTR amyloidosis will be differentiated by DNA analysis;
- 18 years or older;
- cardiac involvement (mean left ventricular wall thickness >12 mm in the absence of other causes);
- history of occurrence of at least 1 event of symptomatic heart failure;
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- stable diuretic dosage for at least 2 weeks before treatment initiation;
- female patients who are postmenopausal for at least 1 year before the screening visit, or are surgically sterile, or if they are of childbearing potential, agree to practice effective methods of contraception from the time of signing the informed consent through 30 days after the last dose of study drug, or agree to completely abstain from intercourse;
- voluntary written consent must be given before performance of any study-related procedure not part of standard medical care with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
Who cannot join
- Subjects must meet none of the following criteria:
- Non-ATTR amyloidosis;
- NYHA class IV;
- enzyme-documented myocardial infarction within 6 months before enrollment;
- pregnant or nursing women;
- uncontrolled bacterial, viral, fungal, HIV, HBV, or HCV infection;
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- presence of other active malignancy with the exception of non-melanoma skin cancer, cervical cancer, treated early-stage prostate cancer provided that prostate specific antigen is within normal limit, or any completely resected carcinoma in situ;
- known allergy to any of the study medications, their analogues, or excipients in the various formulations;
- treatment with drugs potentially affecting doxycycline absorption;
- significant acute gastrointestinal symptoms;
- active peptic ulceration and/or esophageal reflux disease;
- treatment with any investigational products within 28 days before the first dose of study drug;
- requirement for other concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered to be investigational;
- any other serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase III Randomized Study of Doxycycline and Tauroursodeoxycholic Acid (Doxy/TUDCA) Plus Standard Supportive Therapy Versus Standard Supportive Therapy Alone in Cardiac Amyloidosis Caused by Transthyretin
Cardiac amyloidosis caused by transthyretin either mutated (in ATTRm amyloidosis) or wildtype (in ATTRwt, formerly senile, amyloidosis) is a rare disease but is diagnosed with increasing frequency thanks to the availability of non-invasive scintigraphy-based means. Cardiac ATTR amyloidosis is characterized by progressive heart failure with a median survival of less than 4 years, and there is no standard treatment for this disease. It was proved that the marketed antibiotic doxycycline (Doxy) disrupts amyloid fibrils in vitro and in animal models synergistically with tauroursodeoxycholic acid (TUDCA). Based on these pre-clinical data, a clinical trial of Doxy/TUDCA in ATTR Amyloidosis (NCT01171859) was conducted.
Treatment was well tolerated and was able to prevent progression of cardiac dysfunction.
- Conditions
- TTR Cardiac Amyloidosis
- Being tested
- Doxycycline and tauroursodeoxycholic acid, Standard of care
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Doxycycline and tauroursodeoxycholic acidDrug
Also called Standard of care therpay
doxycicline and tauroursodeoxycholic acid
Standard of careDrug
Standard of care
| Study group | Role | What they receive |
|---|---|---|
| Doxy/TUDCA | Experimental | doxycicline (100 mg / BID)
tauroursodeoxycholic acid (250 mg / TID) Receives: Drug: Doxycycline and tauroursodeoxycholic acid |
| Standard of care | Active comparator | Standard of care therapies. Receives: Drug: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
evaluate the efficacy of Doxy/TUDCA in patients with cardiac ATTR amyloidosis, comparing survival free at 18 months of patients receiving Doxy/TUDCA + standard supportive therapy with that of patients in standard supportive therapy alone.
Doxy/TUDCA efficacy
Measured: 18 MONTHS
Secondary outcomes (1)
Compare overall survival at 18 and 30 months of patients receiving Doxy/TUDCA in addition to standard supportive therapy with that of patients receiving standard supportive therapy alone.
Survival
Measured: 18 and 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2018
- Study start11 Apr 2018
- Primary completion18 Jan 2023
- Study completion22 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TTR Cardiac AmyloidosisStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Policlinico San Matteo di PaviaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di Pavia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giovanni Palladini, Fondazione IRCCS Policlinico San Matteo di Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03481972
- Sponsor's protocol ID
- AC 011 IT
- Status last verified
- Jul 2024
- First submitted
- 16 Mar 2018
- Last updated
- 11 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomized Study of Doxycycline and Tauroursodeoxycholic Acid (Doxy/TUDCA) Plus Standard Supportive Therapy Versus Standard Supportive Therapy Alone in Cardiac Amyloidosis Caused by Transthyretin
- ClinicalTrials.gov ID
- NCT03481972
- Acronym / sponsor ID
- AC 011 IT
- Conditions
- TTR Cardiac Amyloidosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di PaviaUniversity, hospital or other
- Study start
- 11 Apr 2018 (actual)
- Primary completion
- 18 Jan 2023 (actual)
- Study completion
- 22 Jun 2023 (actual)
- First posted
- 29 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cardiac amyloidosis caused by transthyretin either mutated (in ATTRm amyloidosis) or wildtype (in ATTRwt, formerly senile, amyloidosis) is a rare disease but is diagnosed with increasing frequency thanks to the availability of non-invasive scintigraphy-based means. Cardiac ATTR amyloidosis is characterized by progressive heart failure with a median survival of less than 4 years, and there is no standard treatment for this disease. It was proved that the marketed antibiotic doxycycline (Doxy) disrupts amyloid fibrils in vitro and in animal models synergistically with tauroursodeoxycholic acid (TUDCA). Based on these pre-clinical data, a clinical trial of Doxy/TUDCA in ATTR Amyloidosis (NCT01171859) was conducted.
Treatment was well tolerated and was able to prevent progression of cardiac dysfunction.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Doxy/TUDCA | Experimental | Drug: Doxycycline and tauroursodeoxycholic aciddoxycicline (100 mg / BID) tauroursodeoxycholic acid (250 mg / TID) |
| Standard of care | Active comparator | Drug: Standard of careStandard of care therapies. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Diagnosis of ATTRwt amyloidosis, or ATTRm p.Ile68Leu and p.Val122Ile;
- the diagnosis of amyloidosis needs to be biopsy-proven, and amyloid deposits need to be characterized as ATTR-type by immuno-electron microscopy or mass spectrometry. Biopsy can be omitted in patients with a positive (score 3) cardiac 99mTc-DPD scintigraphy, provided serum and urine immunofixation does not show monoclonal components. Wild-type and mutated ATTR amyloidosis will be differentiated by DNA analysis;
- 18 years or older;
- cardiac involvement (mean left ventricular wall thickness >12 mm in the absence of other causes);
- history of occurrence of at least 1 event of symptomatic heart failure;
Key exclusion criteria (14 listed)
- Non-ATTR amyloidosis;
- NYHA class IV;
- enzyme-documented myocardial infarction within 6 months before enrollment;
- pregnant or nursing women;
- uncontrolled bacterial, viral, fungal, HIV, HBV, or HCV infection;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Doxycycline and tauroursodeoxycholic acidAlso: Standard of care therpaydoxycicline and tauroursodeoxycholic acid | Drug | Doxy/TUDCA |
| Standard of careStandard of care | Drug | Standard of care |
Primary outcome
evaluate the efficacy of Doxy/TUDCA in patients with cardiac ATTR amyloidosis, comparing survival free at 18 months of patients receiving Doxy/TUDCA + standard supportive therapy with that of patients in standard supportive therapy alone.
Time frame: 18 MONTHS
Doxy/TUDCA efficacy
1 secondary outcome
Compare overall survival at 18 and 30 months of patients receiving Doxy/TUDCA in addition to standard supportive therapy with that of patients receiving standard supportive therapy alone.
Time frame: 18 and 30 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Doxycycline and tauroursodeoxycholic acid in people with TTR Cardiac Amyloidosis, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
evaluate the efficacy of Doxy/TUDCA in patients with cardiac ATTR amyloidosis, comparing survival free at 18 months of patients receiving Doxy/TUDCA + standard supportive therapy with that of patients in standard supportive therapy alone. (time frame: 18 MONTHS). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2024.