Treatment in patients with recurrent infections and IgG Subclass Deficiency, and/or Deficient Anti-Polysaccharide Antibody Response.

There is no consensus on the treatment of patients with recurrent infections
and isolated IgG-subclass deficiency and/or selective antipolysaccharide
antibody deficiency. Therefore, the Dutch Inter University Working Party
intends to start a study in which the treatment with antibiotics will be
compared with intravenous immunoglobulin therapy with respect to clinical
outcome measures in both children and adults with this disorder.

The primary objective of the study is to compare the efficacy of intravenous
immunoglobulin product with the efficacy of antibiotic treatment in patients
with recurrent respiratory infections and IgG-subclass deficiency and/or
selective anti-polysaccharide antibody deficiency, and to define a treatment
protocol for this group of patients.
The secondary objective of the study is to compare the safety of intravenous
immunoglobulin product with the safety of antibiotic treatment in this patient
group.

All patients in this open, prospective multi-centre randomized cross-over study
will be observed during a period of 2 x 12 months separated by a washout period
of 3 months.

In the study period that patients are treated with intravenous immunoglobulin,
Nanogam will be administered in the following dosages:
• Adults: 600 mg/kg bodyweight every 3 weeks
• Children: 800 mg/kg bodyweight every 3 weeks

In the study period that patients are treated with antibiotics, Co-trimoxazol
(trimethoprim/sulfamethoxazol) will be administered in the following dosages:
• Adults and children >=12 years or >=40 kg: 160 mg trimethoprim and 800 mg
sulfamethoxazol once daily, every day of the week combined with 5 mg folic
acid.
If not tolerated well: azitromycin 500 mg once daily, every other day, 3 days
of the week.
• Children >=5-12: 4 mg trimethoprim and 20 mg sulfamethoxazol per kg bodyweight
once daily, every day of the week (max160/800mg/day), combined with 5 mg
folicacid.
If not well tolerated: azitromycin 10 mg per kg bodyweight once daily, every
other day, 3 days a week (max 500 mg /day).

Nanogam and co-trimoxazol are both products with marketing authorization. From
the experience with these products, no risks can be expected. The patient
itself has no direct benefit by this clinical trial, but in the future, the
patient itself and other patients will have the benefit of a treatment protocol
for patients with these disorders.
The extra burden for the patient is limited, since a lot of the blood samplings
and tests would also be performed without participation in the study because of
their disease. At study entry, after 15 months (cross-over), and the end of the
study (after 27 months) a physical examination and some tests (X-ray,
optionally CT-scan, lung function,ENT examination) will be performed.
In total, 50-70 ml blood will be taken during the screening, and 30-50 ml
during the subsequent visits. The patient will visit the clinic every 3 months
(ten visits in 27 months). In case of infections, the visit frequency will be
increased, and cultures will be performed.
The patients have to enter all details on the use of Nanogam (out-patient
clinic or home treatment) and co-trimoxazol (home treatment) in a patient*s
diary. Before each Nanogam infusion a serum sample will be taken to analyze the
IgG trough level.
The end of the study the patient will be asked to fill out a short
questionnaire to evaluate both treatments.