Hyper-reactive Malarial SplenomegalyPhase 3LiHMSNCT01785979
Prednisone Plus Chloroquine for the Treatment of Hyper-reactive Malarial Splenomegaly
A Phase 3 study testing prednisone induction - chloroquine and Chloroquine in people with Hyper-reactive Malarial Splenomegaly and Malaria, run by Lihir Medical Centre at 1 site in Papua New Guinea.
Trial summary
This randomized clinical trial will address a complication related to recurrent episodes of malaria in endemic areas - hyper-reactive malarial splenomegaly. We aim to assess the efficacy of chloroquine after prednisone-induction therapy compared to standard treatment of chloroquine alone in the treatment of adult… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyper-reactive Malarial Splenomegaly, Malaria, Anaemia
- What is being tested?
- prednisone induction - chloroquine and Chloroquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 sitePapua New Guinea
- Study dates
- Jan 2016to Feb 2017
- 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
- Defining features of HMS including chronic massive splenomegaly (at least 10 cm below the costal margin); serum Immunoglobulin M elevated more than 3.1 g/L and high malarial antibody titres (above 640).
- Evidence of the polyclonal nature of the lymphocytes by serum immunoglobulin free light chains.
- Aged at least 18 years
- Haemoglobin level of > 5 mg/d
Who cannot join
- known allergy to chloroquine,
- use of anti-malarial treatment within the preceding month,
- suspected coexisting diseases in which glucocorticoids are contraindicated (e.g. diabetes mellitus, peptic ulcer disease or any acute infection as defined clinically), and
- splenomegaly secondary to known infectious or haematological causes
Trial locations and contacts
1 site in 1 country.
Papua New Guinea1 site
Lihir medical Centre
Londolovit, New Ireland Province
About this study
Official title: Prednisone Plus Chloroquine Versus Chloroquine for the Treatment of Hyper-reactive Malarial Splenomegaly in Papua New Guinea: a Randomized Open-label Trial
This randomized clinical trial will address a complication related to recurrent episodes of malaria in endemic areas - hyper-reactive malarial splenomegaly. We aim to assess the efficacy of chloroquine after prednisone-induction therapy compared to standard treatment of chloroquine alone in the treatment of adult patients with newly diagnosed hyper-reactive malarial splenomegaly.
Read the detailed description
Hyper-reactive malarious splenomegaly (HMS) is a known chronic autoimmune complication in areas where malaria is endemic. Patients with HMS complain most commonly of abdominal swelling or pain from the enlarged spleen and the condition is defined using clear clinical and laboratory criteria. HMS appears benign in most patients when seen first but if untreated, it leads to severe anaemia and also acute bacterial infections. There is familiar and ethnic clustering suggesting genetic basis. High prevalence rates have been reported in certain areas of Papua New Guinea, and Venezuela, and HMS is also common in parts of sub-Saharan Africa, including Sudan and Ghana.
The treatment of HMS is still empirical since no randomized trials have been done so far. Long term anti-malarial chemoprophylaxis is deemed the mainstay of therapy, but the optimal drug-regimen and duration are unknown. Three to six months may pass before a response is observed, and relapses may occur when therapy is discontinued.
On the basis of the observed benefit in experimental studies, glucocorticoids have been used for severe hyper-reactive malarial splenomegaly in various case reports. Because these cases had a favourable outcome and the drug tolerability was good, prednisone has become an attractive therapeutic option for this disease. Central to the pathophysiology of HMS is the overproduction of Immunoglobulin M due to a functional CD8 T-cell defect and the consequent expansion and activation of B lymphocytes. Glucocorticoids may have an immediate effect due to inhibition of the sequestration of immunoglobulin coated red blood cells by the mononuclear phagocyte system and a later effect due to glucocorticoid-induced inhibition of antibody synthesis. We aim to assess the efficacy of chloroquine after prednisone-induction therapy compared to chloroquine alone in the treatment of adult patients with newly diagnosed hyper-reactive malarial splenomegaly.
- Conditions
- Hyper-reactive Malarial Splenomegaly, Malaria, Anaemia
- Being tested
- prednisone induction - chloroquine, Chloroquine
- Medical subject headings
- Malaria, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
prednisone induction - chloroquineDrug
Also called Deltasone,, Orasone,, Prednicen-M
At study entry, the patients will undergo physical examination and laboratory tests, including blood cell count, malaria microscopy, immune-chromatographic test for malaria antigen, malaria serology titers, and serum protein studies with immunoglobulin M quantification, immune-fixation and immunoglobulin free light chains measurement. We will assess all participants at 1, 3, 6 and 12 months after enrollment. Clinical examination and routine laboratory tests are done every 3 months during the follow-up period. Immunoglobulin M quantification and malaria serology are done at baseline, and at month 12 visit.
ChloroquineDrug
Also called Aralen, Resochin, Alchroquin
At study entry, the patients will undergo physical examination and laboratory tests, including blood cell count, malaria microscopy, immune-chromatographic test for malaria antigen, malaria serology titers, and serum protein studies with immunoglobulin M quantification, immune-fixation and immunoglobulin free light chains measurement. We will assess all participants at 1, 3, 6 and 12 months after enrollment. Clinical examination and routine laboratory tests are done every 3 months during the follow-up period. Immunoglobulin M quantification and malaria serology are done at baseline, and at month 12 visit.
| Study group | Role | What they receive |
|---|---|---|
| Prednisone induction - chloroquine | Experimental | 0.5 mg/Kg daily of prednisone for 4 weeks after randomization, 0.25 mg daily for weeks 5-6, 0.15 mg daily for week 7 and 2.5 mg daily for week 8 and chloroquine at a fixed dose (300 mg base per week) for months 1-12 Receives: Drug: prednisone induction - chloroquine |
| chloroquine | Active comparator | chloroquine at a fixed dose (300 mg base per week) for months 1-12 Receives: Drug: Chloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
composite clinical & immunological endpoint
Clinical cure, defined as a sustained reduction in spleen size of at least 40% at the 12 month follow up examination, compared with the spleen size at the baseline examination. Immunological cure, defined as a two-fold decrease of total immunoglobulin M levels is also needed.
Measured: 12 months
Secondary outcomes (5)
3 months intermediate clinical cure
Reduction in spleen size of at least 40% at the 3 month follow up examination
Measured: 3 months
6 months intermediate clinical cure
Reduction in spleen size of at least 40% at the 3 month follow up examination
Measured: 6 months
Anaemia
Incidence of HMS related-anemia defined by hemoglobin levels below 10 g/L at 12 months
Measured: 12 months
Malaria episode
occurrence of an acute episode of malaria identified by passive-case detection in the hospital facilities during the follow up period.
Measured: 12 months
Bacterial infection
occurrence of an acute bacterial infection identified by passive-case detection in the hospital facilities during the follow up period.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2013 (estimated)
- Study startJan 2016
- Primary completionFeb 2017 (estimated)
- Study completionFeb 2017 (estimated)
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hyper-reactive Malarial SplenomegalyStudies of the same condition, open and under way.
- 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lihir Medical Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Oriol Mitja, Lihir Medical Centre
- Investigators
- Oriol Mitja, PhD, Principal investigator, Lihir Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01785979
- Sponsor's protocol ID
- LiHMS
- Acronym
- LiHMS
- Status last verified
- Nov 2015
- First submitted
- 5 Feb 2013
- Last updated
- 13 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prednisone Plus Chloroquine Versus Chloroquine for the Treatment of Hyper-reactive Malarial Splenomegaly in Papua New Guinea: a Randomized Open-label Trial
- ClinicalTrials.gov ID
- NCT01785979
- Acronym / sponsor ID
- LiHMS / LiHMS
- Conditions
- Hyper-reactive Malarial Splenomegaly, Malaria, Anaemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Lihir Medical CentreUniversity, hospital or other
- Study start
- Jan 2016
- Primary completion
- Feb 2017 (estimated)
- Study completion
- Feb 2017 (estimated)
- First posted
- 7 Feb 2013 (estimated)
- 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.
This randomized clinical trial will address a complication related to recurrent episodes of malaria in endemic areas - hyper-reactive malarial splenomegaly. We aim to assess the efficacy of chloroquine after prednisone-induction therapy compared to standard treatment of chloroquine alone in the treatment of adult patients with newly diagnosed hyper-reactive malarial splenomegaly.
Detailed description
Hyper-reactive malarious splenomegaly (HMS) is a known chronic autoimmune complication in areas where malaria is endemic. Patients with HMS complain most commonly of abdominal swelling or pain from the enlarged spleen and the condition is defined using clear clinical and laboratory criteria. HMS appears benign in most patients when seen first but if untreated, it leads to severe anaemia and also acute bacterial infections. There is familiar and ethnic clustering suggesting genetic basis. High prevalence rates have been reported in certain areas of Papua New Guinea, and Venezuela, and HMS is also common in parts of sub-Saharan Africa, including Sudan and Ghana.
The treatment of HMS is still empirical since no randomized trials have been done so far. Long term anti-malarial chemoprophylaxis is deemed the mainstay of therapy, but the optimal drug-regimen and duration are unknown. Three to six months may pass before a response is observed, and relapses may occur when therapy is discontinued.
On the basis of the observed benefit in experimental studies, glucocorticoids have been used for severe hyper-reactive malarial splenomegaly in various case reports. Because these cases had a favourable outcome and the drug tolerability was good, prednisone has become an attractive therapeutic option for this disease. Central to the pathophysiology of HMS is the overproduction of Immunoglobulin M due to a functional CD8 T-cell defect and the consequent expansion and activation of B lymphocytes. Glucocorticoids may have an immediate effect due to inhibition of the sequestration of immunoglobulin coated red blood cells by the mononuclear phagocyte system and a later effect due to glucocorticoid-induced inhibition of antibody synthesis. We aim to assess the efficacy of chloroquine after prednisone-induction therapy compared to chloroquine alone in the treatment of adult patients with newly diagnosed hyper-reactive malarial splenomegaly.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prednisone induction - chloroquine | Experimental | Drug: prednisone induction - chloroquine0.5 mg/Kg daily of prednisone for 4 weeks after randomization, 0.25 mg daily for weeks 5-6, 0.15 mg daily for week 7 and 2.5 mg daily for week 8 and chloroquine at a fixed dose (300 mg base per week) for months 1-12 |
| chloroquine | Active comparator | Drug: Chloroquinechloroquine at a fixed dose (300 mg base per week) for months 1-12 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Defining features of HMS including chronic massive splenomegaly (at least 10 cm below the costal margin); serum Immunoglobulin M elevated more than 3.1 g/L and high malarial antibody titres (above 640).
- Evidence of the polyclonal nature of the lymphocytes by serum immunoglobulin free light chains.
- Aged at least 18 years
- Haemoglobin level of > 5 mg/d
Key exclusion criteria (4 listed)
- known allergy to chloroquine,
- use of anti-malarial treatment within the preceding month,
- suspected coexisting diseases in which glucocorticoids are contraindicated (e.g. diabetes mellitus, peptic ulcer disease or any acute infection as defined clinically), and
- splenomegaly secondary to known infectious or haematological causes
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 |
|---|---|---|
| prednisone induction - chloroquineAlso: Deltasone,, Orasone,, Prednicen-MAt study entry, the patients will undergo physical examination and laboratory tests, including blood cell count, malaria microscopy, immune-chromatographic test for malaria antigen, malaria serology titers, and serum protein studies with immunoglobulin M quantification, immune-fixation and immunoglobulin free light chains measurement. We will assess all participants at 1, 3, 6 and 12 months after enrollment. Clinical examination and routine laboratory tests are done every 3 months during the follow-up period. Immunoglobulin M quantification and malaria serology are done at baseline, and at month 12 visit. | Drug | Prednisone induction - chloroquine |
| ChloroquineAlso: Aralen, Resochin, AlchroquinAt study entry, the patients will undergo physical examination and laboratory tests, including blood cell count, malaria microscopy, immune-chromatographic test for malaria antigen, malaria serology titers, and serum protein studies with immunoglobulin M quantification, immune-fixation and immunoglobulin free light chains measurement. We will assess all participants at 1, 3, 6 and 12 months after enrollment. Clinical examination and routine laboratory tests are done every 3 months during the follow-up period. Immunoglobulin M quantification and malaria serology are done at baseline, and at month 12 visit. | Drug | chloroquine |
Primary outcome
composite clinical & immunological endpoint
Time frame: 12 months
Clinical cure, defined as a sustained reduction in spleen size of at least 40% at the 12 month follow up examination, compared with the spleen size at the baseline examination. Immunological cure, defined as a two-fold decrease of total immunoglobulin M levels is also needed.
5 secondary outcomes
3 months intermediate clinical cure
Time frame: 3 months
6 months intermediate clinical cure
Time frame: 6 months
Anaemia
Time frame: 12 months
Malaria episode
Time frame: 12 months
Bacterial infection
Time frame: 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2015.
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.
Oriol Mitja, PhD principal investigator
Lihir Medical Centre
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 prednisone induction - chloroquine and Chloroquine in people with Hyper-reactive Malarial Splenomegaly and Malaria, run by Lihir Medical Centre at 1 site in Papua New Guinea.
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 4 inclusion and 4 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: withdrawn, as of the sponsor's last update on 13 Nov 2015. 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 Papua New Guinea. 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 was withdrawn before enrolling participants, so there are no results.
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?
composite clinical & immunological endpoint (time frame: 12 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 13 Nov 2015.