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ANCA Associated VasculitisPhase 4HAVENNCT04316494

Hydroxychloroquine in ANCA Vasculitis Evaluation

A Phase 4 study testing Hydroxychloroquine in people with ANCA Associated Vasculitis and Microscopic Polyangiitis, run by Guy's and St Thomas' NHS Foundation Trust at 18 sites in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to find out whether hydroxychloroquine, in addition to background treatments, reduces disease activity in patients with Anti-Neutrophilic Cytoplasmic Autoantibodies (ANCA) Vasculitis, a group of autoimmune diseases. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Hydroxychloroquine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
43 participants
Where
18 sitesUnited Kingdom
Study dates
17 Dec 2020to 15 May 2025
Phase
Phase 4
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

  • Are at least 18 years of age at screening.
  • Have a clinical diagnosis of Granulomatosis Polyangiitis (GPA) or a diagnosis of Microscopic Polyangiitis (MPA) or a diagnosis of Eosinophilic Granulomatosis with Polyangiitis (EGPA) according to the Chapel Hill criteria.
  • Have a Birmingham Vasculitis Activity Score >3 BVAS v.3 (Appendix 2) with minor BVAS items only (no major BVAS items).BVAS should be >3 at screening and at randomisation.
  • Patients should be receiving maintenance therapy at a stable dose for 4 weeks prior to randomisation. Maintenance therapy is defined as prednisolone and/or azathioprine, methotrexate, mycophenolate, co-trimoxazole or maintenance rituximab therapy.
  • Patients receiving corticosteroids for reasons other than vasculitis must be on a stable regimen for four weeks prior to randomisation.
  • A female patient is eligible to enter the study if she is:
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  • Not pregnant or nursing; OR Of non-childbearing potential (i.e., women who have had a hysterectomy, are postmenopausal defined as ≥1 year without menses, have both ovaries surgically removed or have documented tubal ligation or other permanent sterilization procedure); OR
  • Of childbearing potential. These women must have a negative urine pregnancy test at screening and at baseline and be using at least one effective method of contraception. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Consistent and correct use of one of the following acceptable methods of birth control for 1 month prior to the start of the study agent, during the study, and 16 weeks after the last dose of study agent:
  • Oral contraceptive, either combined or progestogen alone Injectable progestogen Implants of levonorgestrel or etonogestrel Estrogenic vaginal ring Percutaneous contraceptive patches Intrauterine device (IUD) or intrauterine system (IUS) with <1% failure rate as stated in the product label
  • No contraindications to hydroxychloroquine therapy.
  • Willing and able to give written informed consent to participate in the trial.
  • Patients should have sufficient English in order to provide informed consent and complete the patient questionnaires.

Who cannot join

  • Patients currently taking hydroxychloroquine or related antimalarial such as mepacrine or chloroquine.
  • Patients with an estimated glomerular filtration rate (eGFR) <30 ml/min.
  • Patients weighing <40kg.
  • Sensitivity, anaphylaxis or allergy to hydroxychloroquine or any other 4-aminoquinoline compound.
  • Known glucose 6 phosphate dehydrogenase deficiency.
  • Known lactose intolerance.
Show all 21Show fewer
  • Evidence of plaque psoriasis.
  • Concomitant use of the following medications within the last six months:
  • Tumour necrosis factor inhibitor treatment (e.g. etanercept) Cyclophosphamide Abatacept Alemtuzumab Any experimental biological therapies Intravenous, intramuscular or sub-cutaneous immunoglobin Plasma exchange Antithymocyte globulin Tamoxifen Live vaccines
  • B cell depleting therapy (rituximab) for remission induction within the last six months. Rituximab maintenance therapy is permitted.
  • Severe or rapidly progressive ANCA vasculitis with at least one major BVAS item.
  • Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to vasculitis (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious disease) which, in the opinion of the principal investigator, could confound the results of the study or put the patient at undue risk.
  • Patients taking long term macrolide antibiotics for a chronic condition. This does not include topical preparations.
  • Have a history of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix.
  • Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to randomisation. A urine drug screen should be performed and confirmed negative prior to study entry.
  • Have a historically positive test or test positive at screening for hepatitis B surface antigen, hepatitis B core antibody or hepatitis C antibody or are known to be HIV-1 positive.
  • Have a Grade 3 or greater laboratory abnormality based on the Common Terminology Criteria for Adverse Events (CTCAE) toxicity scale (version 5), unless considered by the investigator to be related to the underlying disease or induction therapy.
  • Screening 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect patient safety or interpretation of study results, including: - QT interval corrected using the same consistent formula at each visit (QTc) > 470 msec for female > 450 msec for male patients demonstrated by at least two ECGs.
  • Participation in any other interventional trial within the last 6 months.
  • Have a current symptomatic COVID-19 infection.
  • Have been admitted to the ICU in the past 6 months due to a COVID-19 infection.

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

United Kingdom18 sites

  • Royal United Hospitals Bath NHS Foundation Trust

    Bath, Somerset, BA1 3NG

  • University Hospitals Sussex NHS Foundation Trust

    Brighton, Sussex, BN2 5BE

  • Cambridge University Hospitals NHS Foundation Trust

    Cambridge, Cambridgeshire, CB2 0QQ

  • Cardiff & Vale University Health Board

    Cardiff, CF14 4XW

  • Epsom and St Helier University Hospitals NHS Trust

    Epsom

  • NHS Highland

    Inverness, Inverness-shire, IV2 3JH

  • University Hospitals of Leicester NHS Trust

    Leicester, Leicestershire, LE3 9QP

  • Liverpool University Hospitals NHS Foundation Trust

    Liverpool, Merseyside, L9 7AL

  • Cwm Taf Morgannwg University Health Board

    Llantrisant

  • Guy's and St Thomas' NHS Foundation Trust

    London, SE1 9RT

  • King's College Hospital NHS Foundation Trust

    London, SE5 9RS

  • Imperial College Healthcare NHS Trust

    London, W12 0HS

  • Oxford University Hospitals NHS Foundation Trust

    Oxford

  • Royal Berkshire NHS Foundation Trust

    Reading, Berkshire, RG1 5AN

  • Surrey and Sussex Healthcare NHS Trust

    Redhill, Surrey, RH1 5RH

  • East and North Hertfordshire NHS Trust

    Stevenage, Hertfordshire, SG1 4AB

  • South Tyneside and Sunderland NHS Foundation Trust

    Sunderland

  • Torbay and South Devon NHS Foundation Trust

    Torquay

Other trials in United Kingdom

About this study

Official title: Hydroxychloroquine in ANCA Vasculitis Evaluation - A Multicentre, Randomised, Double-blind, Placebo-controlled Trial

The purpose of this study is to find out whether hydroxychloroquine, in addition to background treatments, reduces disease activity in patients with Anti-Neutrophilic Cytoplasmic Autoantibodies (ANCA) Vasculitis, a group of autoimmune diseases.

Hydroxychloroquine and is an established, effective, safe and inexpensive therapy, widely used in other autoimmune diseases such as lupus and rheumatoid arthritis.

Read more

The study is open to adults diagnosed with certain types of vasculitis, called Granulomatosis Polyangiitis (GPA), Microscopic Polyangiitis (MPA) or Eosinophilic Granulomatosis with Polyangiitis (EGPA). Participants will be eligible if they are treated with background medication to control their vasculitis disease and have a low level of disease activity as defined by a Birmingham Vasculitis Activity Score (BVAS) of greater than 3.

Participants will be randomly placed in 1 of 2 groups. Both groups will be given background medication. One group will receive hydroxychloroquine and the other will receive placebo. Participants will be on treatment for 1 year.

76 ANCA Vasculitis participants will be recruited (38 in each treatment arm) from UK vasculitis specialist centres.

Read the detailed description

This is a multi-centre, randomised, placebo-controlled, double-blind study to evaluate if hydroxychloroquine in combination with background maintenance therapy improves the clinical response and quality of life in patients with AAV. 76 participants who have Granulomatosis with Polyangiitis, Microscopic Polyangiitis or Eosinophilic Granulomatosis with Polyangiitis will be recruited from 20 sites.

They will be randomised in a 1:1 ratio of hydroxychloroquine or placebo. Neither the patient nor the research team will know which treatment group the participant is in.

Once the participant agrees to take part and has signed informed consent, they will undergo the following assessments, tests and procedures to find out if they can take part in the study. Some may be routinely done by the study doctor as part of regular vasculitis care even if the participants are not in the study:

  • Medical history
  • Birmingham Vasculitis Activity Score (BVAS)
  • Physical exam
  • Blood tests
  • Pregnancy test
  • Urine drug test
  • Electrocardiogram

If the patient is eligible to take part in the study, they will be randomised to receive either hydroxychloroquine or placebo in addition to background medication. Participants will receive 2 tablets to take once a day over the course of a year. Participants may have their dose reduced to 1 tablet dependent on their weight at baseline and renal function. All participants will have their prednisolone dose tapered down over the course of the study. Participants will be asked to fill in a patient diary on a weekly basis to record whether they've taken their medication, and if they've experienced any change of symptoms.

Participants will be asked to attend the hospital at weeks 4, 16, 28, 40, 44, 48, 52 and 56. At each of these visits, participants will undertake some or all of the following tests/assessments:

  • Physical exam including visual acuity
  • Weight and vital signs
  • BVAS assessment and Vasculitis Damage Index (VDI)
  • Patient questionnaires
  • If there are any changes to their medicines and health status
  • If they experiencing any side effects
  • Blood samples and urine tests to see how the study drug is affecting the body.
  • At two visits, participants will also be asked to undergo an electrocardiogram (ECG).

Patients will be followed up by phone in weeks 10, 22, and 34. This phone call will be based on the ANCA-associated Vasculitis Patient Reported Outcome (AAV PRO) questionnaire and patients will also be encouraged to report any adverse events. Patients reporting new or worsening symptoms will be invited to the hospital for an unscheduled visit.

In addition to clinical bloods, 76ml of blood will be taken for research purposes for all participants. These will be taken at the same time as clinical bloods to minimise discomfort for the participant. Participants at Guy's and St Thomas' will have an additional 200ml of blood taken for isolation of cells. These bloods will be stored and kept for future research, with the written consent of the participant.

Being tested
Hydroxychloroquine, Placebo
Keywords
Granulomatosis Polyangiitis, Eosinophilic Granulomatosis with Polyangiitis
Medical subject headings
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Microscopic Polyangiitis, Churg-Strauss Syndrome, Granulomatosis with Polyangiitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HydroxychloroquineDrug

    Also called Plaquenil

    White, round, film-coated tablets marked 'HCQ' on one side and 200' on the other side.

    Excipients:

    Lactose monohydrate Maize Starch Magnesium Stearate Polyvidone Opadry OY-L-28900

  • PlaceboDrug

    Also called Control

    Placebo to match Hydroxychloroquine.

    Excipients:

    Microcrystalline cellulose Lactose Magnesium Stearate

Study groups in NCT04316494
Study groupRoleWhat they receive
HydroxychloroquineExperimentalPatients will receive 400mg of Hydroxychloroquine (2 x 200mg) to take daily for 52 weeks. Hydroxychloroquine will be started at a dose of 200mg an up-titrated after the first week to a maximum daily dose of 400mg. Patients weighing <50kg, or those patients with an eGFR of 30-50mL/min, will receive a reduced dose of 200mg daily.
Receives: Drug: Hydroxychloroquine
PlaceboPlacebo comparatorPatients will receive 400mg of Placebo (2 x 200mg) to take daily for 52 weeks. Placebo will be started at a dose of 200mg an up-titrated after the first week to a maximum daily dose of 400mg. Patients weighing <50kg, or those patients with an eGFR of 30-50mL/min, will receive a reduced dose of 200mg daily.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The percentage of patients with • uncontrolled AAV disease activity OR • controlled AAV disease activity but prednisolone dose >7.5mg daily OR • controlled AAV disease activity but any corticosteroid use >7.5mg daily for any reason

    The primary endpoint will be the percentage of patients with:

    EITHER

    • uncontrolled AAV disease activity (defined as BVAS > 3) OR
    • controlled AAV disease activity (BVAS ≤ 3) but prednisolone dose >7.5mg daily OR
    • controlled AAV disease activity (BVAS ≤ 3) but any corticosteroid use >7.5mg daily for any reason at any point during the final 12 weeks (±7 days) of the study.

    Inhaled corticosteroids will not contribute to the primary endpoint, nor will methylprednisolone given for rituximab maintenance therapy.

    Measured: BVAS will be assessed during the final 12 (±7 days) weeks that the patient is on the study drug in the trial.

Secondary outcomes (12)

  1. Cumulative number of visits BVAS = 0

    Excluding screening, baseline and week 56

    Measured: Week 4 through to week 52

  2. Proportion of patients with treatment failure at week 52

    As above

    Measured: Week 52

  3. Cumulative prednisolone dosage

    As above

    Measured: From date of randomisation through to week 56 follow up

  4. Total number of adverse events

    As above

    Measured: From date of randomisation through to week 56 follow up

  5. Total number of infections per patient

    As above

    Measured: From date of randomisation through to week 56 follow up

  6. Total number of vasculitis flares (severe and limited) per patient

    As above

    Measured: From date of randomisation through to week 56 follow up

  7. Time to remission

    As above

    Measured: From date of randomisation through to week 56 follow up

  8. Time to first severe flare

    Patients will be categorized as having a severe flare if they have a new or worsening major item on the BVAS.

    Proportion of patients with a limited disease flare defined as having a new or worsening minor BVAS item with no major items at each time point outlined in the trial flowchart.

    Measured: From date of randomisation through to week 56 follow up

  9. Time to first limited flare

    Patients will be categorized as having a limited flare if they have a new or worsening minor item on the BVAS with no new major items.

    Measured: From date of randomisation through to week 56 follow up

  10. Proportion of patients categorized as having a severe flare at each of the time points in the trial schedule excluding screening, baseline and week 56

    As above

    Measured: Weeks 1-52 excluding screening, baseline and week 56

  11. Proportion of patients categorized as having a limited flare at each of the time points in the trial schedule excluding screening, baseline and week 56

    As above

    Measured: Weeks 1-52 excluding screening, baseline and week 56

  12. Absolute values and relative change from baseline in the Vasculitis Damage Index (VDI) at each time point outlined in the trial schedule.

    As above

    Measured: From date of randomisation through to week 56 follow up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2020
  2. Study start17 Dec 2020
  3. Primary completion15 May 2025
  4. Study completion15 May 2025

Why it stopped: Recruitment was terminated early by the funder due to study sites' inability to recruit sufficient number of participants.

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04316494
Sponsor's protocol ID
251987
Other IDs
2018-001268-40, 2018
Acronym
HAVEN
Status last verified
Apr 2026
First submitted
25 Feb 2020
Last updated
29 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: N/A - no plan to share identifiable patient data with other researchers.

Publications

  • Learoyd AE, Arnold L, Reid F, Beckley-Hoelscher N, Casian A, Sangle S, Morton N, Nel L, Cape A, John S, Kim S, Shivapatham D, Luqmani R, Jayne D, Galloway J, Douiri A, D'Cruz D; HAVEN study group. The HAVEN study-hydroxychloroquine in ANCA vasculitis evaluation-a multicentre, randomised, double-blind, placebo-controlled trial: study protocol and statistical analysis plan. Trials. 2023 Apr 6;24(1):261. doi: 10.1186/s13063-023-07108-3.

    PubMed 37024906

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Hydroxychloroquine in people with ANCA Associated Vasculitis and Microscopic Polyangiitis, run by Guy's and St Thomas' NHS Foundation Trust at 18 sites in United Kingdom.

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 12 inclusion and 21 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: stopped early, as of the sponsor's last update on 29 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United Kingdom. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 was stopped early (reason given: Recruitment was terminated early by the funder due to study sites' inability to recruit sufficient number of participants.). Results are not available in the source record.

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?

The percentage of patients with • uncontrolled AAV disease activity OR • controlled AAV disease activity but prednisolone dose >7.5mg daily OR • controlled AAV disease activity but any corticosteroid use >7.5mg daily for any reason (time frame: BVAS will be assessed during the final 12 (±7 days) weeks that the patient is on the study drug in the trial.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04316494, which also lists 1 linked publication.

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 29 Apr 2026.

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