Clinical Trial Results:
HERO:Hydroxychloroquine Effectiveness in Reducing Symptoms of hand OA, a randomised, double-blind, placebo-controlled trial
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Summary
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EudraCT number |
2011-004300-38 |
Trial protocol |
GB |
Global end of trial date |
18 Oct 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Oct 2020
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First version publication date |
30 Oct 2020
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Other versions |
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Summary report(s) |
HERO EOT report |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
RR10/9390
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
University of Leeds
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Sponsor organisation address |
Worsley Building, Leeds, United Kingdom, LS2 9JT
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Public contact |
Sarah Kingsbury, University of Leeds, s.r.kingsbury@leeds.ac.uk
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Scientific contact |
Sarah Kingsbury, University of Leeds, s.r.kingsbury@leeds.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Oct 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Oct 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Oct 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary question to be answered by this study is whether hydroxychloroquine is an effective treatment for relieving pain in hand OA.
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Protection of trial subjects |
sign Overview
HERO was an investigator-led, pragmatic, multicenter, superiority, randomized, 1:1 placebo-controlled
trial. The research protocol (Part 1 of the Supplement,
available at Annals.org) was approved by the Leeds
East Research Ethics Committee and the U.K. Medicines and Healthcare Products Regulatory Agency and
registered on ISRCTN (ISRCTN91859104). Participants
were recruited from 24 September 2012 until 27 May
2014 and followed up for 12 months after randomization (follow-up completed 25 April 2015). All participants gave written informed consent before screening.
One was recruited before protocol registration (24
September 2012 vs. 17 October 2012); however, no
changes were made to the protocol between these
time points, so this participant is similar to all others
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Background therapy |
Synovitis is believed to play a role in producing symptoms in persons with hand osteoarthritis, but data on slowacting anti-inflammatory treatments are sparse.Symptomatic hand osteoarthritis affects 4% to 31% of adults older than 70 years and 3% to 15% older than 60 years (1–7). Patients report chronic persistent pain and considerable difficulty with daily activities (8). However, few therapies are effective, and their use is often limited by patients' comorbid conditions or toxicities (9 –11). Consequently, primary and secondary care physicians seek alternatives to improve quality of life for persons with this painful, disabling disease. Anecdotal reports suggest hydroxychloroquine (HCQ) as one such therapy. It has been used as an unlicensed treatment in many countries when other options have failed, mainly for patients with “inflammatory” hand osteoarthritis (12, 13). An established drug treatment of inflammatory arthritides, such as rheumatoid arthritis (RA), HCQ is supported by placebo-controlled trials showing its efficacy (as monotherapy and in combination with other RA drugs) and acceptable safety profile (14, 15). Increasing evidence that inflammation is prevalent in osteoarthritis and may have a role in symptoms (16 –20) and 3 small pilot studies suggesting reduction in hand pain with HCQ (21–23) provide a rationale for exploring the efficacy of HCQ in treating hand osteoarthritis. The objective of the HERO (Hydroxychloroquine Effectiveness in Reducing symptoms of hand Osteoarthritis) trial was to test the hypothesis that HCQ is an effective symptomatic treatment when used in persons with at least moderate symptomatic hand osteoarthritis and an inadequate response to current therapies, including nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jun 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 248
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Worldwide total number of subjects |
248
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EEA total number of subjects |
248
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
134
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From 65 to 84 years |
112
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85 years and over |
2
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Recruitment
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Recruitment details |
Participants were recruited from 24 September 2012 until 27 May 2014 and followed up for 12 months after randomization (follow-up completed 25 April 2015). All participants gave written informed consent before screening. | |||||||||
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Pre-assignment
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Screening details |
Participants were recruited from 24 September 2012 until 27 May 2014 and followed up for 12 months after randomization (follow-up completed 25 April 2015). All participants gave written informed consent before screening. | |||||||||
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Period 1
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Period 1 title |
Main Trial Period (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Data analyst | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Hydroxychloroquine 6.5mg per day | |||||||||
Arm description |
HCQ 200, 300, or 400 mg, with dosage calculated according to ideal body weight for a maximum of 6.5 mg/kg per day | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Hydroxychloroquine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
200, 300, or 400 mg, with dosage calculated according to ideal body weight for a maximum of 6.5 mg/kg
per day
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Arm title
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Placebo | |||||||||
Arm description |
Placebo arm | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Identical to IMP used in intervention arm
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Baseline characteristics reporting groups
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Reporting group title |
Hydroxychloroquine 6.5mg per day
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Reporting group description |
HCQ 200, 300, or 400 mg, with dosage calculated according to ideal body weight for a maximum of 6.5 mg/kg per day | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo arm | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Hydroxychloroquine 6.5mg per day
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Reporting group description |
HCQ 200, 300, or 400 mg, with dosage calculated according to ideal body weight for a maximum of 6.5 mg/kg per day | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo arm | ||
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End point title |
s average hand pain during the previous 2 weeks (on a 0- to 10-point numerical rating scale [NRS]) at 6 months [1] | ||||||||||||
End point description |
: The primary end point was average hand pain
during the previous 2 weeks (on a 0- to 10-point numerical rating
scale [NRS]) at 6 months. Secondary end points included selfreported pain and function, grip strength, quality of life, radiographic structural change, and adverse events. Baseline ultrasonography was done.
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End point type |
Primary
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End point timeframe |
6 Months
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Please see attached results paper for all details of all final assessment patient figures, and statistical analysis performed in the trial. |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
Staff asked participants about AEs at all visits, and physicians reviewed
AEs for severity, duration, and relatedness to the investigational medicinal product.
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Adverse event reporting additional description |
Serious AEs were defined
according to prespecified criteria, as detailed in the
protocol (Part 1 of the Supplement); assessed for causality and expectedness by a physician; and reported
within 24 hours.
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||
Dictionary version |
4.0
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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Please see attached results paper for all details of Adverse Event Data |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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18 Jul 2012 |
Amendment 2 |
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18 Sep 2012 |
Amendment 4 |
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20 Dec 2012 |
Amendment 5 |
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28 Jun 2013 |
Amendment 7 |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
