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Report for Clinical Trial NCT03768908

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Multicentre Randomised Comparative Clinical Trial of the Efficacy of Artesunate + Amodiaquine Versus Artemether-lumefantrine (Coartem®) for the Treatment of Uncomplicated Childhood Plasmodium Falciparum Malaria in Zanzibar

The primary objective of the study was to determine the PCR-APCR up to day 42 in children <60 months of age, weighing ≥5kg with uncomplicated malaria, treated with either artesunate+ amodiaquine (ASAQ) or artemether-lumefantrine (AL; Coartem®). Secondary objectives included: clinical and laboratory assessment of drug tolerability and safety, evaluation of possible correlation between drug bioavailability and clinical outcome, comparison of efficacy data with the pre-implementation "ACO I" study, parasite and fever clearance, gametocyte carriage, and possible selection of mutations related to quinoline resistance.

NCT03768908 Plasmodium Falciparum Malaria
MeSH:Malaria Malaria, Falciparum

2 Interventions

Name: Artemether-lumefantrine

Description: Three day treatment with Artemether-lumefantrine, 2 doses a day under direct observation
Type: Drug
Group Labels: 1

Treatment with artemether-lumefantrine (Coartem®)

Name: Artesunate + Amodiaquine

Description: Three day treatment with Artesunate + Amodiaquine, co-administered, a dose a day under direct observation
Type: Drug
Group Labels: 1

Treatment with artesunate + amodiaquine


Primary Outcomes

Description: Comparing PCR adjusted parasitological cure rate (PCR-APCR) between the two treatment options up to day 42. Parasitological cure will be adjusted using PCR genotyping of msp2 marker. Recrudescence is defined as the presence of at least one matching allelic band, and reinfection as the absence of any matching allelic band on day 0 and day of recurring parasitaemia. Patients with recurrent parasitaemia having missing filter paper sample or negative PCR results will be considered uncertain with regards to PCR adjusted outcome.

Measure: PCR adjusted parasitological cure rates by day 42

Time: 42 days

Secondary Outcomes

Description: Comparing proportion of response outcomes according to standard WHO classification i.e., cure rates on days 14, day 28 and 42. Defined as the absence of both re-parasitaemia and clinical symptoms suggestive of severe malaria during follow-up to the respective days.

Measure: The clinical and parasitological response outcome (i.e. cure rates) on days 14, day 28 and 42.

Time: 42 days

Other Outcomes

Description: Proportion of patients reporting any adverse event (AE) in the two study arms. The intensity of an adverse event was determined according to the following definitions: mild, moderate, severe, unknown. AEs were be categorized according to if there is a likely causal relationship between the event and the medical products: probably, possibly, unlikely.

Measure: Clinical and laboratory assessment of drug tolerability and safety i.e., incidence of adverse events.

Time: 42 days

Description: Fever clearance was determined by a medical doctor/officer who measured the patient's axillary temperature using an electronic thermometer and took a detailed clinical history as well as performed a clinical examination. All details were recorded in the CRF.

Measure: Fever clearance in the two study arms

Time: 42 days

Description: Clearance of parasites and gametocyte carriage were determined by Giemsa stained thick blood films were examined using electrical or sunlight microscope at the study site by an experienced microscopist. The number of parasites were calculated as the number of parasites seen against 200 leucocytes in the thick blood film and recorded in the CRF for the correct occasion. The slides were stored for quality controls, 10% of all slides were double-checked centrally.

Measure: Parasite clearance and gametocyte carriage in the two study arms

Time: 42 days

Description: Proportions of single nucleotide polymorphisms at pfmdr1 Y86N and pfcrt K76T determined by established AluI restriction-based PCR-RFLP.

Measure: Proportion of mutations related to Quinoline resistance at day0 and day of recurrent infection in the two study arms

Time: 42 days

Purpose: Treatment

Allocation: Randomized


There are 2 SNPs

SNPs


1 K76T

Proportions of single nucleotide polymorphisms at pfmdr1 Y86N and pfcrt K76T determined by established AluI restriction-based PCR-RFLP.. Inclusion Criteria: - Weight ≥5kg - No general danger signs or severe malaria present (see 4.4.2.1 & 4.4.2.2) - History of fever within 24 hours OR axillary temperature ≥ 37.5Cº - No other cause of fever is detectable - No severe malnutrition - Patient has parasite counts between 2000-200,000/ul (50-5000/200 white blood cells) - Guardian/Patient has understood the procedures of the study and is willing to participate - Patient able to come for stipulated follow up visits and has easy access to the Study Site Exclusion Criteria: General Danger Signs and Complications: - Not able to drink or breastfeed - Vomiting everything - Recent history of convulsions - Lethargic or unconscious - Unable to sit or stand (as appropriate for age) - History of allergy to test drugs - History of intake of any drugs other than paracetamol and aspirin within 3 days Signs of Severe Malaria: - Altered consciousness - Repeated convulsions - Inability of oral intake - Severe anaemia (Hb <5gm/dl) - Difficulty in breathing (pulmonary oedema, Respiratory Distress Syndrome) - Shock (small pulse, cold extremities) - Hypoglycaemia - Haemoglobinuria (dark coloured urine or Coca-Cola urine) - Kidney failure (little or no urine in a well-hydrated patient) - Jaundice (yellow colouring of eyes) - Hyperpyrexia (temperature above 39.5ºC) in combination with other signs - Hyperparasitaemia (more than 5% red blood cells parasitized or >200,000 parasites/µl) - Spontaneous bleeding (Disseminated Intravascular Coagulation) Inclusion Criteria: - Weight ≥5kg - No general danger signs or severe malaria present (see 4.4.2.1 & 4.4.2.2) - History of fever within 24 hours OR axillary temperature ≥ 37.5Cº - No other cause of fever is detectable - No severe malnutrition - Patient has parasite counts between 2000-200,000/ul (50-5000/200 white blood cells) - Guardian/Patient has understood the procedures of the study and is willing to participate - Patient able to come for stipulated follow up visits and has easy access to the Study Site Exclusion Criteria: General Danger Signs and Complications: - Not able to drink or breastfeed - Vomiting everything - Recent history of convulsions - Lethargic or unconscious - Unable to sit or stand (as appropriate for age) - History of allergy to test drugs - History of intake of any drugs other than paracetamol and aspirin within 3 days Signs of Severe Malaria: - Altered consciousness - Repeated convulsions - Inability of oral intake - Severe anaemia (Hb <5gm/dl) - Difficulty in breathing (pulmonary oedema, Respiratory Distress Syndrome) - Shock (small pulse, cold extremities) - Hypoglycaemia - Haemoglobinuria (dark coloured urine or Coca-Cola urine) - Kidney failure (little or no urine in a well-hydrated patient) - Jaundice (yellow colouring of eyes) - Hyperpyrexia (temperature above 39.5ºC) in combination with other signs - Hyperparasitaemia (more than 5% red blood cells parasitized or >200,000 parasites/µl) - Spontaneous bleeding (Disseminated Intravascular Coagulation) Plasmodium Falciparum Malaria Malaria Malaria, Falciparum All children in the right age group presenting with clinical signs of malaria at the study site were considered possible study subjects. --- Y86N --- --- K76T ---

The pfmdr1 Y86N and pfcrt K76T genes' Single Nucleotide Proteins (SNPs) analysis was done according to established AluI restriction-based PCR-RFLP protocols. --- Y86N --- --- K76T ---


2 Y86N

Proportions of single nucleotide polymorphisms at pfmdr1 Y86N and pfcrt K76T determined by established AluI restriction-based PCR-RFLP.. Inclusion Criteria: - Weight ≥5kg - No general danger signs or severe malaria present (see 4.4.2.1 & 4.4.2.2) - History of fever within 24 hours OR axillary temperature ≥ 37.5Cº - No other cause of fever is detectable - No severe malnutrition - Patient has parasite counts between 2000-200,000/ul (50-5000/200 white blood cells) - Guardian/Patient has understood the procedures of the study and is willing to participate - Patient able to come for stipulated follow up visits and has easy access to the Study Site Exclusion Criteria: General Danger Signs and Complications: - Not able to drink or breastfeed - Vomiting everything - Recent history of convulsions - Lethargic or unconscious - Unable to sit or stand (as appropriate for age) - History of allergy to test drugs - History of intake of any drugs other than paracetamol and aspirin within 3 days Signs of Severe Malaria: - Altered consciousness - Repeated convulsions - Inability of oral intake - Severe anaemia (Hb <5gm/dl) - Difficulty in breathing (pulmonary oedema, Respiratory Distress Syndrome) - Shock (small pulse, cold extremities) - Hypoglycaemia - Haemoglobinuria (dark coloured urine or Coca-Cola urine) - Kidney failure (little or no urine in a well-hydrated patient) - Jaundice (yellow colouring of eyes) - Hyperpyrexia (temperature above 39.5ºC) in combination with other signs - Hyperparasitaemia (more than 5% red blood cells parasitized or >200,000 parasites/µl) - Spontaneous bleeding (Disseminated Intravascular Coagulation) Inclusion Criteria: - Weight ≥5kg - No general danger signs or severe malaria present (see 4.4.2.1 & 4.4.2.2) - History of fever within 24 hours OR axillary temperature ≥ 37.5Cº - No other cause of fever is detectable - No severe malnutrition - Patient has parasite counts between 2000-200,000/ul (50-5000/200 white blood cells) - Guardian/Patient has understood the procedures of the study and is willing to participate - Patient able to come for stipulated follow up visits and has easy access to the Study Site Exclusion Criteria: General Danger Signs and Complications: - Not able to drink or breastfeed - Vomiting everything - Recent history of convulsions - Lethargic or unconscious - Unable to sit or stand (as appropriate for age) - History of allergy to test drugs - History of intake of any drugs other than paracetamol and aspirin within 3 days Signs of Severe Malaria: - Altered consciousness - Repeated convulsions - Inability of oral intake - Severe anaemia (Hb <5gm/dl) - Difficulty in breathing (pulmonary oedema, Respiratory Distress Syndrome) - Shock (small pulse, cold extremities) - Hypoglycaemia - Haemoglobinuria (dark coloured urine or Coca-Cola urine) - Kidney failure (little or no urine in a well-hydrated patient) - Jaundice (yellow colouring of eyes) - Hyperpyrexia (temperature above 39.5ºC) in combination with other signs - Hyperparasitaemia (more than 5% red blood cells parasitized or >200,000 parasites/µl) - Spontaneous bleeding (Disseminated Intravascular Coagulation) Plasmodium Falciparum Malaria Malaria Malaria, Falciparum All children in the right age group presenting with clinical signs of malaria at the study site were considered possible study subjects. --- Y86N ---

The pfmdr1 Y86N and pfcrt K76T genes' Single Nucleotide Proteins (SNPs) analysis was done according to established AluI restriction-based PCR-RFLP protocols. --- Y86N ---



HPO Nodes