Prednisone Plus Chloroquine for the Treatment of Hyper-reactive Malarial Splenomegaly

NCT ID: NCT01785979

Last Updated: 2015-11-13

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2017-02-28

Brief 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 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.

Conditions

Hyper-reactive Malarial Splenomegaly; Malaria; Anaemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Prednisone induction - chloroquine

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

Group Type: EXPERIMENTAL

prednisone induction - chloroquine

Intervention Type: DRUG

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.

chloroquine

chloroquine at a fixed dose (300 mg base per week) for months 1-12

Group Type: ACTIVE_COMPARATOR

Chloroquine

Intervention Type: DRUG

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.

Interventions

prednisone induction - chloroquine

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.

Intervention Type: DRUG

Chloroquine

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.

Intervention Type: DRUG

Other Intervention Names

Deltasone,; Orasone,; Prednicen-M; Aralen; Resochin; Alchroquin

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lihir Medical Centre

OTHER

Sponsor Role: lead

Responsible Party

Oriol Mitja

Senior Medical Officer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Oriol Mitja, PhD

Role: PRINCIPAL_INVESTIGATOR

Lihir Medical Centre

Locations

Lihir medical Centre

Londolovit, New Ireland Province, Papua New Guinea

Countries

Papua New Guinea

Other Identifiers

LiHMS

Identifier Type: -

Identifier Source: org_study_id