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

Condition(s) targeted: Hyper-reactive Malarial Splenomegaly; Malaria; Anaemia

Intervention: prednisone induction - chloroquine (Drug); Chloroquine (Drug)

Phase: Phase 3

Status: Not yet recruiting

Sponsored by: Lihir Medical Centre

Official(s) and/or principal investigator(s):
Oriol Mitja, PhD, Principal Investigator, Affiliation: Lihir Medical Centre

Overall contact:
Oriol Mitja, PhD, Phone: +6759867188, Email: oriolmitja@hotmail.com

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.

Official title: Prednisone Plus Chloroquine Versus Chloroquine for the Treatment of Hyper-reactive Malarial Splenomegaly in Papua New Guinea: a Randomized Open-label Trial

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: composite clinical & immunological endpoint

Secondary outcome:

3 months intermediate clinical cure

6 months intermediate clinical cure

Anaemia

Malaria episode

Bacterial infection

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Oriol Mitja, PhD, Phone: +6759867188, Email: oriolmitja@hotmail.com

Lihir medical Centre, Londolovit, New ireland province, Papua New Guinea; Active, not recruiting

Starting date: January 2016
Last updated: March 31, 2015