Here is the design of a clinical trial:

Official Title: Short-course Benznidazole Treatment to Reduce Trypanosoma Cruzi Parasitic Load in Women of Reproductive Age: A Non-inferiority Randomized Controlled Trial

Included conditions:
- Chagas Disease

Study Armgroups:
- {'label': '60/300mg', 'type': 'ACTIVE_COMPARATOR', 'description': 'The investigators will use a preparation of benznidazole (BZN) that is commercially available in Argentina: Abarax® 100mg and 50mg tablets from ELEA laboratories (Buenos Aires, Argentina). The investigators will purchase the drug at full cost.\n\nInterventions: The standard 60d course will be 300 mg per day, which is similar to the dose used in the second phase of the BENEFIT trial. The drug will be administered orally in two doses per day: the standard course will be one 100mg and one 50mg tablet in the morning and in the evening for 60 days.', 'interventionNames': ['Drug: Benznidazole']}
- {'label': '30/150mg', 'type': 'EXPERIMENTAL', 'description': 'The investigators will use a preparation of benznidazole (BZN) that is commercially available in Argentina: Abarax® 100mg and 50mg tablets from ELEA laboratories (Buenos Aires, Argentina). ELEA laboratories will prepare the placebo oral tablets, which will be identical to the drug tablets in aspect and taste. The investigators will purchase the drug and placebo at full cost.\n\nInterventions: The BZN short course low dose scheme will be 150 mg per day for 30 days. The drug will be administered orally in two doses per day: the short course treatment will start with the active drug and then placebo oral tablet; one 100 mg tablet and one placebo tablet in the morning and one 50 mg tablet and one placebo tablet in the evening for the first 30 days. The last 30 days will be two placebo tablets in the morning and the evening.', 'interventionNames': ['Drug: Benznidazole', 'Drug: Placebo Oral Tablet']}

Interventions:
- {'type': 'DRUG', 'name': 'Benznidazole', 'description': 'Benznidazole tablet', 'armGroupLabels': ['30/150mg', '60/300mg'], 'otherNames': ['Abarax']}
- {'type': 'DRUG', 'name': 'Placebo Oral Tablet', 'description': 'Sugar pill manufactured to mimic Benznidazole', 'armGroupLabels': ['30/150mg'], 'otherNames': ['Placebo (for Benznidazole)']}

Primary Outcomes:
- {'measure': 'Frequency of positive PCR and the parasitic load measured by qPCR immediately after BZN 30d/150mg', 'description': 'The frequency of positive PCR and the parasitic load measured by qPCR immediately after BZN 30d/150mg will be non-inferior (Non Inferiority \\[NI\\] margin for PCR: 10% absolute difference) to BZN 60d/300mg.', 'timeFrame': '30 days for the 30d course arm, and 60 days for the 60d course arm'}
- {'measure': 'The frequency of positive PCR and the parasitic load measured by qPCR 10 months after BZN 30d/150mg', 'description': 'The frequency of positive PCR and the parasitic load measured by qPCR immediately after BZN 30d/150mg will be non-inferior (Non Inferiority \\[NI\\] margin for PCR: 10% absolute difference) to BZN 60d/300mg.', 'timeFrame': '10 months from the end of the 60d treatment'}

Please estimate the sample size based on the assumption: 
The significance level is set at α = 0.025 for the non-inferiority hypothesis and α = 0.05 for the superiority hypothesis. The power is set at 90% for detecting non-inferiority and more than 80% for detecting a reduction in serious adverse events. A 10% loss to follow-up rate is assumed.
Sample size
        For Specific Aim 1 and following Food Drug Administration (FDA) and CONSORT guidance, we estimated that the NI margin should preserve 75% of the effect of 60d/300âmg (considered as 100%) over placebo (considered as 0%) found in previous trials [29, 44]. The primary outcome is the frequency of positive T. cruzi PCR.
        We estimated an effect on PCR conversion to negative with BZN 60d of 80 and 30% with placebo. This is supported by: 1) the observed effects of BZN and placebo in the BENEFIT study in Argentina and Bolivia, which showed conversion rates from a positive to a negative PCR of 73.0% in the BZN 60d group and 28.6% in the placebo group at the end of treatment [17] and 2) the therapeutic response to BZN treatment is better in young and healthy subjects than in older subjects with cardiomyopathy (see 1.2.2 Drug of choice for preconceptional treatment). We will enroll mostly healthy young women (median 23âyears old), compared to the older subjects (mean 55âyears old) with cardiomyopathy participating in the BENEFIT study. We used the 78.4% positive PCR rate at delivery we found in our previous study in TucumÃ¡n, Argentina [48].
        Based on these figures, we estimated a frequency of positive PCR of 15% (0.78(1â0.8)) after BZN 60d/300âmg and of 55% (0.78(1â0.3)) after placebo. To preserve 75% of the BZN 60d/300âmg effect over placebo (40% absolute rate difference), the NI margin will be 10.0% absolute rate difference. For the 10-month follow-up aim (Hypothesis 1b), we expect that after almost 1 year, the PCR positive rates will be up to 20% higher, as shown in the BENEFIT study [17]. The NI margin preserving 75% of the effect will be 9% in this case. TableÂ 3 shows that we will need to enroll nearly 540âT. cruzi seropositive women. With this sample size, we will have adequate power to detect non-inferiority with a NI margin preserving 75% of the effect of the 60d course over placebo if the PCR rates following treatment are higher than expected, or for preserving 70% if a 3% difference in PCR rates between arms is found. To protect from a potential 10% loss to follow-up at 10âmonths, we will enroll 600 women.
Table 3Statistical power and sample size assessment for specific aim 1a for nÂ =â268 subjects per group (NÂ =â536 total subjects)60da(%)30da(%)Placeboa(%)Effect sizea(%)Proportion retainedNI margina(%)Power(%)15.015.055.040.00.7510.09018.018.055.034.00.759.38015.018.055.040.00.7012.080aCells show PCR positive rate
        For Specific Aim 2, we postulated a superiority hypothesis. The rate of serious adverse events leading to treatment interruption observed in the BENEFIT trial was 24%. As mentioned above, our population is healthier and younger; thus, we will conservatively assume a 20% rate. We will have more than 90% power to detect a reduction of serious adverse events and/or any adverse event leading to treatment interruption from 20% in the 60d course group to 10% in the short course group (TableÂ 4) and more than 80% power if the rate is 12%. The two-sided Type I error rate was set at Î±â=â0.025 and 0.05 for the NI and superiority hypotheses respectively, and calculations were carried out with the power sample size calculator for a two-sample non-inferiority study with a sampling ratio of one [49].
Table 4Statistical power assessment for specific aim 2 (superiority hypothesis)60d(%)30d(%)Total(N)Power(%)201060095201260081