Trial Outcomes & Findings for A Three Day Trial of Azithromycin Plus Chloroquine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria (NCT NCT00282919)
NCT ID: NCT00282919
Last Updated: 2014-06-26
Results Overview
Parasite clearance was defined as the clearance of asexual Plasmodium falciparum (P falciparum) parasitemia (defined as three consecutive 0 parasite counts) within 7 days of initiation of treatment, without subsequent recrudescence up to Day 28. Failure to achieve clearance of asexual P falciparum parasitemia was defined as parasitemia not cleared within 7 days of initiation of treatment, or subsequent recrudescence (confirmed by molecular testing) by Day 28 after achieving clearance. Percentage of participants with clearance is reported. Here "N" (Number of participants analyzed) signify participants who were evaluable (parasitological per protocol) at Day 28.
COMPLETED
PHASE2
110 participants
Day 28
2014-06-26
Participant Flow
Participant milestones
| Measure |
Azithromycin and Chloroquine
Four azithromycin 500 milligram (mg) tablets (equivalent to 2000 mg) orally once daily along with 2 chloroquine 300 mg base tablets (equivalent to 600 mg) orally once daily for 3 days.
|
|---|---|
|
Overall Study
STARTED
|
110
|
|
Overall Study
COMPLETED
|
103
|
|
Overall Study
NOT COMPLETED
|
7
|
Reasons for withdrawal
| Measure |
Azithromycin and Chloroquine
Four azithromycin 500 milligram (mg) tablets (equivalent to 2000 mg) orally once daily along with 2 chloroquine 300 mg base tablets (equivalent to 600 mg) orally once daily for 3 days.
|
|---|---|
|
Overall Study
Lack of Efficacy
|
4
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Asymptomatic Parasitemia
|
2
|
Baseline Characteristics
A Three Day Trial of Azithromycin Plus Chloroquine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria
Baseline characteristics by cohort
| Measure |
Azithromycin and Chloroquine
n=110 Participants
Four azithromycin 500 milligram (mg) tablets (equivalent to 2000 mg) orally once daily along with 2 chloroquine 300 mg base tablets (equivalent to 600 mg) orally once daily for 3 days.
|
|---|---|
|
Age, Continuous
|
30.8 years
STANDARD_DEVIATION 13.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
85 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 28Population: Parasitological per protocol (PP) population: Participants who had study drug for 3 days unless treatment failure, no concomitant anti-malarial unless designated treatment failure, had test of cure at Day 28, baseline smear with parasitemia between 1000-100000 parasites/microliter, rapid diagnostic test positive for P falciparum, history of fever.
Parasite clearance was defined as the clearance of asexual Plasmodium falciparum (P falciparum) parasitemia (defined as three consecutive 0 parasite counts) within 7 days of initiation of treatment, without subsequent recrudescence up to Day 28. Failure to achieve clearance of asexual P falciparum parasitemia was defined as parasitemia not cleared within 7 days of initiation of treatment, or subsequent recrudescence (confirmed by molecular testing) by Day 28 after achieving clearance. Percentage of participants with clearance is reported. Here "N" (Number of participants analyzed) signify participants who were evaluable (parasitological per protocol) at Day 28.
Outcome measures
| Measure |
Azithromycin and Chloroquine
n=107 Participants
Four azithromycin 500 milligram (mg) tablets (equivalent to 2000 mg) orally once daily along with 2 chloroquine 300 mg base tablets (equivalent to 600 mg) orally once daily for 3 days.
|
|---|---|
|
Percentage of Participants With Parasite Clearance at Day 28
|
97.20 percentage of participants
Interval 94.09 to 100.0
|
SECONDARY outcome
Timeframe: Baseline up to Day 28Population: Parasitologic PP population. Here, "N" (Number of participants analyzed) signifies those who were evaluable for this outcome measure.
ETF was defined as a participant meeting any of these criteria: development of signs of severe malaria (impaired consciousness \[for example, obtundation, unarousable coma, delirium, stupor\], respiratory distress \[respiratory rate greater than or equal to {\>=} 30 breaths/minute\], seizures, hypoglycemia \[glucose less than or equal to {\<=} 40 milligram/deciliter\], gross hematuria, increase in parasitemia to greater than 100,000 parasites/microliter in 48 hours or later after the first treatment dose was administered) any day from Day 0 to 3 in the presence of P falciparum parasitemia; parasite count on Day 2 \> Day 0 (baseline), irrespective of axillary or oral temperature; parasite count on Day 3 \> 37.5 degrees Celsius (axillary temperature) and \>38 degrees Celsius (oral temperature) and parasite count on Day 3 \>=25 percent (%) of the first available parasite density on Day 0 (baseline).
Outcome measures
| Measure |
Azithromycin and Chloroquine
n=107 Participants
Four azithromycin 500 milligram (mg) tablets (equivalent to 2000 mg) orally once daily along with 2 chloroquine 300 mg base tablets (equivalent to 600 mg) orally once daily for 3 days.
|
|---|---|
|
Percentage of Participants With Early Treatment Failures (ETF)
|
0 percentage of participants
Interval -0.47 to 0.47
|
SECONDARY outcome
Timeframe: Baseline up to Day 28Population: Parasitologic PP population. Here, "N" (Number of participants analyzed) signifies those who were evaluable for this outcome measure.
LTF included late clinical failure (LCF) and late parasitologic failure (LPF). LCF is defined as a participant meeting any of these criteria: development of signs or symptoms of severe malaria after Day 3 in the presence of P falciparum parasitemia, without previously meeting any of the criteria of ETF or presence of P falciparum parasitemia and fever or history of fever on any day from Day 4 to Day 28, without previously meeting any of the criteria of ETF. LPF is defined as presence of P falciparum parasitemia on any day from Day 7 to Day 28 and the absence of fever or history of fever without previously meeting any of the criteria of ETF or LCF.
Outcome measures
| Measure |
Azithromycin and Chloroquine
n=107 Participants
Four azithromycin 500 milligram (mg) tablets (equivalent to 2000 mg) orally once daily along with 2 chloroquine 300 mg base tablets (equivalent to 600 mg) orally once daily for 3 days.
|
|---|---|
|
Percentage of Participants With Late Treatment Failures (LTF)
|
2.80 percentage of participants
Interval -0.3 to
The upper limit of 90% CI was not estimable because very few participants had response.
|
SECONDARY outcome
Timeframe: Days 7, 14, 21, 28, 35, 42Population: Parasitologic PP population. Here, "N" (Number of participants analyzed) signifies those who were evaluable for this outcome measure and "n" signifies number of participants who were evaluated at given time point.
Resistance is measured by clearance of asexual P falciparum parasitemia and categorized into 3 levels; resistance I (RI): clearance of asexual P. falciparum parasitemia before Day 7 followed by recurrence on or after Day 7, resistance II (RII): marked reduction (\<=25% of baseline) of asexual P. falciparum parasitemia but no clearance prior to and up to Day 7, and resistance III (RIII): no marked reduction (\>25% of baseline) of asexual P. falciparum parasitemia. Recurrence was defined as the reappearance of asexual P. falciparum parasitemia following a quiescent or latent period after the cessation of the primary attack. Percentage of participants with resistance as measured by RI, RII and RIII is reported.
Outcome measures
| Measure |
Azithromycin and Chloroquine
n=109 Participants
Four azithromycin 500 milligram (mg) tablets (equivalent to 2000 mg) orally once daily along with 2 chloroquine 300 mg base tablets (equivalent to 600 mg) orally once daily for 3 days.
|
|---|---|
|
Percentage of Participants With Resistance to Treatment
Day 42 (n=107)
|
25.23 percentage of participants
|
|
Percentage of Participants With Resistance to Treatment
Day 7 (n=109)
|
22.02 percentage of participants
|
|
Percentage of Participants With Resistance to Treatment
Day 14 (n=109)
|
22.02 percentage of participants
|
|
Percentage of Participants With Resistance to Treatment
Day 21 (n=107)
|
22.43 percentage of participants
|
|
Percentage of Participants With Resistance to Treatment
Day 28 (n=107)
|
24.3 percentage of participants
|
|
Percentage of Participants With Resistance to Treatment
Day 35 (n=107)
|
25.23 percentage of participants
|
SECONDARY outcome
Timeframe: Day 3, 7, 28, and 42Population: Parasitologic PP population. Here, "N" (Number of participants analyzed) signifies those who were evaluable for this outcome measure.
Clinical Cure is defined as resolution of the participant's fever and other symptoms attributed to P falciparum malaria (for example, abdominal pain, malaise, and headache).
Outcome measures
| Measure |
Azithromycin and Chloroquine
n=109 Participants
Four azithromycin 500 milligram (mg) tablets (equivalent to 2000 mg) orally once daily along with 2 chloroquine 300 mg base tablets (equivalent to 600 mg) orally once daily for 3 days.
|
|---|---|
|
Percentage of Participants With Clinical Cure
Day 3
|
100.00 percentage of participants
Interval 99.54 to 100.0
|
|
Percentage of Participants With Clinical Cure
Day 7
|
100.00 percentage of participants
Interval 99.54 to 100.0
|
|
Percentage of Participants With Clinical Cure
Day 28
|
96.33 percentage of participants
Interval 92.9 to 99.77
|
|
Percentage of Participants With Clinical Cure
Day 42
|
96.33 percentage of participants
Interval 92.9 to 99.77
|
SECONDARY outcome
Timeframe: Day 7, 14, 21, 35, 42Population: Parasitologic PP population. Here, "N" (Number of participants analyzed) signifies those participants who were evaluable for this outcome measure and "n" signifies number of participants who were evaluated at given time point.
Parasite clearance was defined as the clearance of asexual Plasmodium falciparum (P falciparum) parasitemia (defined as three consecutive 0 parasite counts) within 7 days of initiation of treatment, without subsequent recrudescence up to Day 28. Failure to achieve clearance of asexual P falciparum parasitemia was defined as parasitemia not cleared within 7 days of initiation of treatment, or subsequent recrudescence (confirmed by molecular testing) by Day 28 after achieving clearance. Percentage of participants with clearance is reported. Here "N" (Number of participants analyzed) signify participants who were evaluable (parasitological per protocol) at Day 28.
Outcome measures
| Measure |
Azithromycin and Chloroquine
n=109 Participants
Four azithromycin 500 milligram (mg) tablets (equivalent to 2000 mg) orally once daily along with 2 chloroquine 300 mg base tablets (equivalent to 600 mg) orally once daily for 3 days.
|
|---|---|
|
Percentage of Participants With Parasite Clearance at Day 7, 14, 21, 35, 42
Day 35 (n=107)
|
96.26 percentage of participants
Interval 92.76 to 99.76
|
|
Percentage of Participants With Parasite Clearance at Day 7, 14, 21, 35, 42
Day 7 (n=109)
|
100.00 percentage of participants
Interval 99.54 to 100.0
|
|
Percentage of Participants With Parasite Clearance at Day 7, 14, 21, 35, 42
Day 14 (n=109)
|
100.00 percentage of participants
Interval 99.54 to 100.0
|
|
Percentage of Participants With Parasite Clearance at Day 7, 14, 21, 35, 42
Day 21 (n=107)
|
99.07 percentage of participants
Interval 97.06 to 100.0
|
|
Percentage of Participants With Parasite Clearance at Day 7, 14, 21, 35, 42
Day 42 (n=107)
|
96.26 percentage of participants
Interval 92.76 to 99.76
|
SECONDARY outcome
Timeframe: Day 7, 14, 21, 28, 35, 42Population: Parasitologic PP population. Here, "N" (Number of participants analyzed) signifies those who were evaluable for this outcome measure and "n" signifies number of participants who were evaluated at given time point.
Gametocyte clearance was defined as clearance of P falciparum gametocytemia (defined as attainment of 3 consecutive 0 gametocyte counts) without subsequent recurrence through the day of consideration. Recurrence was defined as the reappearance of asexual P. falciparum gametocytemia after achieving clearance. Percentage of participants with gametocyte clearance were reported.
Outcome measures
| Measure |
Azithromycin and Chloroquine
n=109 Participants
Four azithromycin 500 milligram (mg) tablets (equivalent to 2000 mg) orally once daily along with 2 chloroquine 300 mg base tablets (equivalent to 600 mg) orally once daily for 3 days.
|
|---|---|
|
Percentage of Participants With Gametocyte Clearance
Day 7 (n=109)
|
84.40 percentage of participants
Interval 78.2 to 90.61
|
|
Percentage of Participants With Gametocyte Clearance
Day 14 (n=109)
|
81.65 percentage of participants
Interval 75.07 to 88.24
|
|
Percentage of Participants With Gametocyte Clearance
Day 21 (n=106)
|
77.35 percentage of participants
Interval 70.17 to 84.55
|
|
Percentage of Participants With Gametocyte Clearance
Day 28 (n=105)
|
76.19 percentage of participants
Interval 68.84 to 83.54
|
|
Percentage of Participants With Gametocyte Clearance
Day 35 (n=103)
|
76.69 percentage of participants
Interval 69.33 to 84.07
|
|
Percentage of Participants With Gametocyte Clearance
Day 42 (n=104)
|
76.92 percentage of participants
Interval 69.61 to 84.23
|
SECONDARY outcome
Timeframe: Baseline up to Day 42Population: Data not possible to report, as clearance time was obtained as life table plots only, as per planned analysis.
Fever clearance time (FCT) was defined as the time from baseline to the first of 2 consecutive time points with temperature less than (\<) 37.5 degree Celsius (C) (axillary temperature) or \<38 degree C (oral temperature).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline up to Day 42Population: Data not possible to report, as clearance time was obtained as life table plots only, as per planned analysis.
Asexual P falciparum parasite clearance time was defined as the time from baseline to the first of the 3 consecutive 0 parasite counts.
Outcome measures
Outcome data not reported
Adverse Events
Azithromycin and Chloroquine
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Azithromycin and Chloroquine
n=110 participants at risk
Four azithromycin 500 milligram (mg) tablets (equivalent to 2000 mg) orally once daily along with 2 chloroquine 300 mg base tablets (equivalent to 600 mg) orally once daily for 3 days.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.91%
1/110
|
|
Cardiac disorders
Tachycardia
|
0.91%
1/110
|
|
Gastrointestinal disorders
Diarrhoea
|
11.8%
13/110
|
|
Gastrointestinal disorders
Gastritis
|
3.6%
4/110
|
|
Gastrointestinal disorders
Nausea
|
32.7%
36/110
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
22/110
|
|
General disorders
Pain
|
0.91%
1/110
|
|
Infections and infestations
Vaginitis bacterial
|
0.91%
1/110
|
|
Infections and infestations
Viral infection
|
0.91%
1/110
|
|
Infections and infestations
Vulvovaginal candidiasis
|
0.91%
1/110
|
|
Metabolism and nutrition disorders
Anorexia
|
0.91%
1/110
|
|
Metabolism and nutrition disorders
Dehydration
|
5.5%
6/110
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.8%
2/110
|
|
Psychiatric disorders
Depressed mood
|
0.91%
1/110
|
|
Psychiatric disorders
Insomnia
|
0.91%
1/110
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.6%
4/110
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER